연구 연혁

(주)알트메디칼 CTO 윤진호 박사(Fouder) 의 미토콘드리아 연구 히스토리를 소개합니다.

2010-2012

1. 암발생과정에서 미토콘드리아 기능이상의 역할 연구

• Kim HJ et al (Acta Biochim Biophys Sin, 2011) DNA 손상이 미토콘드리아 생합성을 억제하는 분자기전 규명
• Song N et al (J Pineal Res, 2012) 멜라토닌의 항암제에 의한 미토콘드리아 기능이상 개선효과 검증

2012-2014

1. 형광단백질 mtKeima를 활용한 미토파지 정량적 측정시스템 개발 (미국 NIH)

2. mtKeima를 발현하는 미토파지 모델 마우스의 제작 및 생체 미토파지 분석연구

• Lee IH et al (Methods Mol Biol, 2012) mtKeima를 활용한 미토파지 측정기법 발표
• Kim AJ (BBRC, 2013) 항암단백질 p21 결손에 의한 미토콘드리아 기능이상 규명
• Yun J, Finkel T (Cell Metab, 2013) 미토콘드리아 스트레스가 세포보호 및 스트레스 저항기전을 유도한다는 ‘Mitohormesis’ 개념 제시

2014-2016

1. 미토파지 모델 초파리 제작

2. 미토파지 유전자 및 미토파지 조절물질 스크리닝 시스템 개발

• Sun N et al (Mol Cell, 2015) 미토파지 모델마우스를 활용한 세계최초 생체 미토파지 분석. 노화 및 질병모델에서 미토파지 활성 변화 검증
• Orloff Innovation Science Award (NIH, USA) 생체미토파지 분석기법 개발공로로 수상
• 미토파지 조절물질 및 조절유전자 스크리닝 시스템 국내특허 출원 (2016.09.27.)

2017-2019

1. 화합물 스크리닝을 통한 미토파지 유도화합물 발굴

2. 화학적 최적화를 통해 임상적용이 가능한 미토파지 촉진화합물 개발

• Um JH, Yun J (BMB Rep, 2017) 인체질병 및 생리기능에서 미토파지 역할 리뷰
• Um JH et al (J Vis Exp, 2018) 유세포분석기 (FACS)를 활용한 미토파지 측정기법 소개
• Kim YY et al (FASEB J, 2019) 초파리 모델 미토파지 분석 및 스트레스 유도 미토파지 활성화에 PINK1-Parkin경로 필요성 세계최초 검증

2020-2021

1. 신규 미토파지 촉진화합물 ALT001의 임상 적합성 검증 및 분자기전 검증연구

2. 추가 미토파지 유도물질 발굴 및 미토파지 조절유전자 기능연구

• Kim YY et al (FASEB J, 2020) 세포노화 과정에서 항암단백질 p53에 의한 미토콘드리아 형태조절의 분자기전 규명
• Lee JH et al (Viruses, 2021) 인플루엔자 바이러스의 감염과정에서 미토파지 조절기능의 중요성 및 분자기전 검증
• ALT001의 미토콘드리아 기능개선 효능 국내특허 출원 (2021.04.21.)

3. 연구소 기업 (주)알트메디칼 창업

2022-2024

1. ALT001의 치매 및 신경퇴행성 질병 치료효능 검증연구

2. 화학적 최적화를 통한 유도체 도출 및 검증 연구

• Lee KM, Yun J (J Genet Med, 2022) 인체질병에서 미토파지 이상 및 치료시도 리뷰
• Um JH et al (Theranostics, 2024)
  • ALT001의 개발: 화합물 라이브러리 스크리닝을 통해 발굴된 Hit 물질의 화학적 최적화를 통해 미토파지 활성이 25배 개선된 ALT001 도출
  • ALT001의 임상적합성 및 분자기전: 기존 미토파지 유도물질 CCCP와는 달리 미토콘드리아 독성, 세포독성을 보이지 않으며, 미토파지만 특이적으로 촉진함. PINK1-Parkin 경로와는 독립적이며, ULK1-Rab9 매개 대체미토파지 경로에 의해 미토파지를 촉진함을 규명함.
  • ALT001의 알츠하이머성 치매 치료기능: 치매동물의 인지기능 회복시험을 세가지 마우스모델로 검증함. 또한, 치매동물 뇌조직의 미토콘드리아 기능을 개선함을 검증함.
• Im S et al (Br J Pharmacol, 2024) 해양생물유래 신규 미토파지 촉진물질 PDE701의 임상적합성 및 항암제유도성 말초신경병증 (CIPN) 치료효과 검증
• Jeong DJ et al (Exp Mol Med, 2024) 미토콘드리아 스트레스에 의한 미토파지 촉진에서 히포경로 핵심인자 Mst1/2의 기능 최초규명 및 치료표적으로서의 가능성 제시
• Oh SJ et al (Cell Death Dis, 2024) 수두대상포진 바이러스 (VZV)의 미토파지 조절을 통한 면역반응 회피 분자기전 규명
• ALT001 신규 유도체들의 물질특허 및 용도특허 국내 및 국제출원 (2022.05.06., 2022.10.11., 2022.10.14., 2022.10.19.)

2025-2026

1. ALT001 기반 치료제 비임상후보 도출을 위한 신약개발 연구

2. 퇴행성 질병에서 미토파지의 중요성 및 분자기전 규명연구

• Oh SJ et al (Theranostics, 2025) 헤르페스 바이러스 (HSV1)의 미토파지 억제에 의한 알츠하이머병 가속화 규명 및 ALT001의 HSV1 감염 저해를 통한 치료효과 검증
• Lee KM et al (Exp Mol Med, 2025) 당뇨병콩팥병 (DKD) 발병에서 미토파지 감소의 중요성 규명 및 신규 미토파지 촉진물질 PDE701의 치료효과 검증
• Im S et al (Sci Rep, 2025) ALT001의 항암제유도성 말초신경병증 (CIPN) 치료효과 검증
• Um JH et al (Sci Rep, 2026) 화학적 최적화에 의한 ALT001의 유도체 ALT001-4a 개발 및 알츠하이머병 치료효능 검증
• ALT001 유도체들의 물질특허 및 용도특허들의 미국, 유럽 및 중국특허 출원 (2025.02.11., 2025.04.15., 2025.04.19.) 적응증: AD, PD, DKD, HSV1 항바이러스, 피부광노화에 대한 주름, 미백, 보습, 항염 개선, 탈모개선 등

논문

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5. 5. Park, M., Chae, H.D., Yun, J., Jung, M., Kim, Y.S., Kim, S.H., Han, M.H. and Shin, D.Y. (2000) Constitutive activation of cyclin B1-associated cdc2 kinase overrides p53-mediated G2-M arrest. Cancer Res. 60: 542-5.
6. 6. Jung, M.*, Yun, J.* , Chae, H.D., Kim, S.C., Choi, T.S. and Shin, D.Y. (2001) p53 and its homologues, p63 and p73, induce replicative senescence through inactivation of NF-Y transcription factor. Oncogene. 20:5818-25 (*Co-first author)
7. 7. Yun, J., Chae, H.D., Choi, T.S., Kim, E.H., Bang, Y.J., Chung, J., Choi, K.S., Mantovani, R., Shin, D.Y. (2003) Cdk2-dependent phosphorylation of the NF-Y transcription factor and its involvement in the p53-p21 signaling pathway. J. Biol Chem. 278(38): 36966-72
8. 8. Yun, J. and Lee, W. H. (2003) Degradation of the transcription repressor ZBRK1 through the ubiquitin-proteasome pathway relieves repression of Gadd45 upon DNA damage. Mol. Cell. Biol. 23(20): 7305-14.
9. 9. Chae, H.D., Yun, J., Bang Y.J., Shin, D.Y. (2004) Cdk2-dependent phosphorylation of the NF-Y transcription factor is essential for expression of the cell cycle-regulatory genes and cell cycle G1/S and G2/M transitions. Oncogene. May 20, 23(23):4084-8
10. 10. Utomo, A., Jian, X., Furuta, S., Yun, J., Levin, D.S., Wang, Y.C., Desai, K. V., Green, J. E., Chen, P. L., Lee, W. H. (2004) Identification of a novel non-selenocysteine containing phospholipid hydroperoxide glutathione peroxidase (NPGPx) essential for alleviating oxidative stress generated from polyunsaturated fatty acids in breast cancer cells. J Biol Chem. Oct 15 279(42):43522-9.
11. 11. Yun, J., Zhong, Q., Kwak, J.Y., Lee, W. H. (2005) Hypersensitivity of Brca1-deficient MEF to DNA interstrand cross-linking agent mitomycin C is associated with defect in homologous recombination repair and aberrant S-phase arrest. Oncogene. June 9; 24(25) 4009-4016.
12. 12. Lee, H.Y., Kim, M.K., Park, K.S., Bae, Y.H., Yun, J., Park, J.I., Kwak, J.Y., Bae, Y.S. (2005) Serum amyloid A stimulates matrix-metalloproteinase-9 activity via formyl peptide receptor like-1-mediated signaling in human monocytic cells. Biochem Biophys Res Commun. 330(3) 989-998.
13. 13. Yun, J. (2005) Involvement of Brca1 in DNA interstrand cross-link repair through homologous recombination-independent process. August 30. J. Life. Sci. 15(4) 542-547.
14. 14. Chae, H.D., Yun, J., Shin, D.Y. (2005) Transcription repression of a CCAAT-binding transcription factor CBF/HSP70 by p53. October 31. Exp Mol Med. 37(5),488-91.
15. 15. Kim MK, Lee HY, Park KS, Shin EH, Jo SH, Yun J , Lee SW, Yoo YH, Lee YS, Baek SH, Bae YS. Lysophosphatidic acid stimulates cell proliferation in rat chondrocytes. Biochem Pharmacol. 2005 Dec 5. 70(12) 1764-1771.
16. 16. Kim MA, Kim H, Yun J., (2006) Impaired Spindle Checkpoint Response of Brca1-deficient Mouse Embryonic Fibroblasts (MEFs) to Nocodazole Treatment. Feb 28. J. Life. Sci. 16(1) 12-16
17. 17. Lee CJ, Han JS, Seo CY, Park TH, Kwon HC, Jeong JS, Kim IH, Yun J , Bae YS, Kwak JY, Park JI. (2006) Pioglitazone, a synthetic ligand for PPARgamma, induces apoptosis in RB-deficient human colorectal cancer cells. Apoptosis , Mar 2, 11(3), 401-411.
18. 18. Kim MK, Lee HY, Kwak JY, Park JI, Yun J , Bae YS. (2006) Sphingosine-1-phosphate stimulates rat primary chondrocyte proliferation. Biochem Biophys Res Commun. Jun 23, 345(1);67-73
19. 19. Jo SH, Yun J , Kim JM, Lee C, Baek SH, Bae YS. (2007) Serum amyloid A induces WISH cell apoptosis. Acta Pharmacol Sin. Jan;28(1):73-80.
20. 20. Kim MK, Park KS, Lee H, Kim YD, Yun J , Bae YS. (2007) Phytosphingosine-1-phosphate stimulates chemotactic migration of L2071 mouse fibroblasts via pertussis toxin-sensitive G-proteins. Exp Mol Med. Apr 30;39(2):185-94.
21. 21. Kim MA, Kim HJ, Brown AL, Lee MY, Bae YS, Park JI, Kwak JY, Chung JH, Yun J . (2007). Identification of novel substrates for human checkpoint kinase Chk1 and Chk2 through genome-wide screening using a consensus Chk phosphorylation motif. Exp Mol Med . Apr 30;39(2):205-12.
22. 22. Lee MY, Kim MA, Kim HJ, Bae YS, Park JI, Kwak JY, Chung JH, Yun J . (2007) Alkylating agent methyl methanesulfonate (MMS) induces a wave of global protein hyperacetylation: Implications in cancer cell death. Biochem Biophys Res Commun . Aug24; 360(2);483-9
23. 23. Park KS, Lee HY, Lee SY, Kim MK, Kim SD, Kim JM, Yun J , Im DS, Bae YS. (2007) Lysophosphatidylethanolamine stimulates chemotactic migration and cellular invasion in SK-OV3 human ovarian cancer cells: Involvement of pertussis toxin-sensitive G-protein coupled receptor. FEBS Lett . 2007 Sep 18;581(23):4411-6.
24. 24. Jo SH, Kim SD, Kim JM, Lee HY, Lee SY, Shim JW, Yun J , Im DS, Bae YS. (2008) Lysophosphatidylserine stimulates chemotactic migration in U87 human glioma cells. Biochem Biophys Res Commun. Jul 18; 372(1), 147-151
25. 24. Lee MY, Kim HJ, Kim MA, Jee HJ, Kim AJ, Bae YS, Park JI, Chung JH, Yun J . (2008) Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation. Cell Cycle , Sept 1, 7(17) 2705-2709.
26. 25. Lee SY, Lee HY, Kim SD, Jo SH, Shim JW, Lee HJ, Yun J , Bae YS. (2008) Lysophosphatidylglycerol stimulates chemotactic migration in human natural killer cells. Biochem Biophys Res Commun Sep12; 374(1), 147-151.
27. 26 Lee HY, Kim SD, Shim JW, Lee SY, Lee H, Cho KH, Yun J , Bae YS. (2008) Serum amyloid A induces CCL2 production via formyl peptide receptor-like 1-mediated signaling in human monocytes. J Immunol. Sep 15, 181(6), 4332-4339.
28. 27. Kim MK, Kim SD, Lee HY, Lee SY, Shim JW, Yun J , Kim JM, Min DS, Yoo YH, Bae YS. (2008) Collagen-binding motif peptide, a cleavage product of osteopontin, stimulates human neutrophil chemotaxis via pertussis toxin-sensitive G protein-mediated signaling. FEBS Lett. Oct 15, 582(23), 3379-84
29. 28. Kim MA, Kim HJ, Jee HJ, Kim AJ, Bae YS, Bae SS, Yun J. (2009) Akt2, but not Akt1, is required for cell survival by inhibiting activation of JNK and p38 after UV irradiation. Oncogene. March 5, 28(9) 1241-7
30. 29. Yun SJ, Tucker DF, Kim EK, Kim MS, Do KH, Ha JM, Lee SY, Yun J , Kim CD, Birnbaum MJ, Bae SS. (2009) Differential regulation of Akt/protein kinase B isoforms during cell cycle progression. FEBS Lett. 2009 Feb 18. 583(4) 685-690
31. 30. Lee HY, Kim SD, Shim JW, Yun J , Kim K, Bae YS. (2009) Activation of formyl peptide receptor like-1 by serum amyloid A induces CCL2 production in human umbilical vein endothelial cells. Biochem Biophys Res Commun. Mar 6;380(2):313-7.
32. 31. Lee HY, Kim SD, Shim JW, Lee SY, Yun J , Bae YS. (2009) LL-37 inhibits serum amyloid A-induced IL-8 production in human neutrophils. Exp Mol Med . May 31: 41(5):325-33.
33. 32. Jee HJ, Kim HJ, Kim AJ, Bae YS, Bae SS, Yun J . (2009) UV light induces premature senescence in Akt1-null mouse embryonic fibroblasts by increasing intracellular levels of ROS. Biochem Biophys Res Commun. June 5, 383(3):358-62. Epub 2009 Apr 11.
34. 33. Shim JW, Jo SH, Kim SD, Lee HY, Yun J , Bae YS. (2009) Lysophosphatidylglycerol inhibits formyl peptide receptorlike-1-stimulated chemotactic migration and IL-1beta production from human phagocytes. Exp Mol Med. Aug 31;41(8):584-91.
35. 34. Kim SD, Kim JM, Jo SH, Lee HY, Lee SY, Shim JW, Seo SK, Yun J , Bae YS. (2009) Functional expression of formyl peptide receptor family in human NK cells. J Immunol. Nov 1;183(9):5511-7.
36. 35. Lee HY, Kim SD, Shim JW, Kim HJ, Yun J , Baek SH, Kim K, Bae YS. (2010) A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production. Exp Mol Med. Apr 30;42(4)302-309.
37. 36. Joe Y, Do MH, Seo E, Kang S, Park HT, Yun J , Lee HJ. (2010) Fenofibrate antagonizes Chk2 activation by inducing Wip1 expression: Implications for cell proliferation and tumorigenesis. Life Sci. 2010 May 8;86(19-20):716-721
38. 37. Jee HJ, Kim AJ, Song N, Kim HJ, Kim M, Koh H, Yun J . (2010) Nek6 overexpression antagonizes p53-induced senescence in human cancer cells. Cell Cycle , Dec 1, 9:23, 4703-4710
39. 38. Yun J , Son CH, Um SJ, Kwon HC, Lee KE, Choi PJ, Roh MS. (2011) A different TRAP220 expression in distinct histologic subtypes of lung adenocarcinoma and the prognostic significance. Lung Cancer , March, 71(3) 312-318
40. 39. Jee HJ, Kim HJ, Kim AJ, Song N, Kim M, Yun J . (2011) Nek6 suppresses the premature senescence of human cancer cells induced by camptothecin and doxorubicin treatment. Biochem Biophys Res Commun , May 20; 408(4):669-73.
41. 40. Kim AJ, Kim HJ, Jee HJ, Song N, Kim M, Bae YS, Chung JH, Yun J . (2011) Glucose deprivation is associated with Chk1 degradation through the ubiquitin-proteosome pathway and effective checkpoint response to replication blocks. Biochim Biophys Acta-Mol Cell Res. Jun, 1813(6): 1230-8
42. 41. Kim EK, Yun SJ, Ha JM, Kim YW, Jin IH, Yun J , Shin HK, Song SH, Kim JH, Lee JS, Kim CD, Bae SS. (2011) Selective activation of Akt1 by mammalian target of rapamycin complex 2 regulates cancer cell migration, invasion, and metastasis. Oncogene. Jun 30;30(26):2954-63
43. 42. Kim HJ, Jee HJ, Yun J . (2011) DNA damage induces downregulation of PEPCK and G6P gene expression through degradation of PGC-1α. Acta Bioch Bioph Sin. August;43(8):589-594.
44. 43. Kim HJ, Roh MS, Son CH, Kim AJ, Jee HJ, Song N, Kim M, Seo SY, Yoo YH, Yun J. (2012) Loss of Med1/TRAP220 promotes the invasion and metastasis of human non-small-cell lung cancer cells by modulating the expression of metastasis-related genes. Cancer Lett. Aug 28;321(2):195-202.
45. 44. Song N, Kim AJ, Kim HJ, Jee HJ, Kim M, Yoo YH, Yun J. (2012) Melatonin suppresses doxorubicin-induced premature senescence of A549 lung cancer cells by ameliorating mitochondrial dysfunction. J Pineal Res. Nov;53(4):335-43.
46. 45. Kim AJ, Jee HJ, Song N, Kim M, Jeong SY, Yun J . (2013) p21WAF1/CIP1 deficiency induces mitochondrial dysfunction in HCT116 colon cancer cells. Biochem Biophys Res Commun , Jan 11, 430(2):653-8.
47. 46. Jee HJ, Kim HJ, Kim AJ, Song N, Kim M, Lee HJ, Yun J . (2013) The inhibition of Nek6 function sensitizes human cancer cells to premature senescence upon serum reduction or anticancer drug treatment. Cancer Lett. 2013 Jul 10;335(1):175-82.
48. 47. Kim JB, Kim SY, Kim B, Lee H, Kim I, Yun J , Jo Y, Oh T, Jo Y, Chae HD, Shin DY. Identification of a novel anti-apoptotic E3 ubiquitin ligase that ubiquitinates antagonists of inhibitor of apoptosis proteins, SMAC, HtrA2 and ARTS. J Biol Chem. 2013 Apr 26;288(17):12014-21.
49. 48. Kim JY, Chung JY, Lee SG, Kim YJ, Park JE, Yun J , Park YC, Kim BG, Yoo YH, Kim JM. p53 interferes with microtubule-stabilizing agent-induced apoptosis in prostate and colorectal cancer cells. Int J Mol Med. 2013 Jun;31(6):1388-1394.
50. 49. Lee IH, Yun J , Finkel T. (2013) The emerging links between sirtuins and autophagy. Methods Mol Biol. 1077:259-71.
51. 50. Yun J . Finkel T. (2014) Mitohormesis. Cell Metab. May 6, 19(5):757-66.
52. 51. Yoo SH, Kim HY, Rho JH, Jeong SY, Yun J , Yun I, Park HT, Yoo YH. Targeted inhibition of mitochondrial Hsp90 induces mitochondrial elongation in Hep3B hepatocellular carcinoma cells undergoing apoptosis by increasing the ROS level. Int J Oncol. 2015 Nov;47(5):1783-92.
53. 52. Sun N*, Yun J *, Liu J, Malide D, Liu C, Rovira I, Holmstrom KM, Fergusson MM, Yoo HY, Combs Ca, Finkel T. (2015) Measuring In Vivo Mitophagy. Mol Cell . Nov 19; 60(4):685-696 (*co-first authors)
54. 53. Kwon KA*, Yun J* , Oh SY, Seo BG, Lee S, Lee JH, Kim SH, Choi HJ, Roh MS, Kim HJ. (2016) Clinical significance of Peroxisome Proliferator-Activated Receptor γ and TRAP220 in Patients with Operable Colorectal Cancer. Cancer Res Treat . 2016 Jan. 48(1):198-207 (*co-first author)
55. 54. Kim M, Kim YY, Jee HY, Bae SS, Jeong NY, Um JH, Yun J . (2016) Akt3 knockdown induces mitochondrial dysfunction in human cancer cells. Acta Bioch Bioph Sin. 2016 May 48(5):447-453.
56. 55. Wagner G, Lindroos-Christensen J, Einwallner E, Husa J, Zapf TC, Lipp K, Rauscher S, Gröger M, Spittler A, Loewe R, Gruber F, Duvigneau JC, Mohr T, Sutterlüty-Fall H, Klinglmüller F, Prager G, Huppertz B, Yun J , Wagner O, Esterbauer H, Bilban M. HO-1 inhibits preadipocyte proliferation and differentiation at the onset of obesity via ROS dependent activation of Akt2. Sci Rep. 2017 Jan 19;7:40881. doi: 10.1038/srep40881. PMID: 28102348
57. 56. Jo SY, Jung IH, Yi JH, Choi TJ, Lee S, Jung JW, Yun J , Lee YC, Ryu JH, Kim DH. Ethanol extract of the seed of Zizyphus jujuba var. spinosa potentiates hippocampal synaptic transmission through mitogen-activated protein kinase, adenylyl cyclase, and protein kinase A pathways. J Ethnopharmacol. 2017 Feb 3. pii: S0378-8741(17)30462-2. doi: 10.1016/j.jep.2017.02.009. [Epub ahead of print] PMID: 28167293
58. 57. Kim HJ, Yun J . Checkpoint-dependent phosphorylation of Med1/TRAP220 in response to DNA damage. Acta Bioch Bioph Sin. 2017 Jun 1;49(6):496-502. doi: 10.1093/abbs/gmx036. PMID: 28430840
59. 58. Um JH, Yun J . Emerging role of mitophagy in human diseases and physiology. BMB Rep. 2017 June 30. 50(6):299-307. PMID: 28366191
60. 59. Kim YY, Jee HY, Um JH, Kim YM, Bae SS, Yun J. Cooperation between p21 and Akt is required for p53-dependent cellular senescence. Aging Cell. 2017. Oct;16(5):1094-1103. PMID: 28691365
61. 60. Kim YY, Yun SH, Yun J . Downregulation of Drp1, a fission regulator, is associated with human lung and colon cancers. Acta Biochim Biophys Sin (Shanghai). 2018 Feb 1;50(2):209-215.
62. 61. Kim, Y. Y., Um, J. H., Yun, J . A Quantitative Measurement of Reactive Oxygen Species and Senescence-associated Secretory Phenotype in Normal Human Fibroblasts During Oncogene-induced Senescence. J. Vis. Exp. (138), e57890, doi:10.3791/57890 (2018).
63. 62. Um, J. H., Kim, Y. Y., Finkel, T., Yun, J . Sensitive Measurement of Mitophagy by Flow Cytometry Using the pH-dependent Fluorescent Reporter mt-Keima. J. Vis. Exp. (138), e58099, doi:10.3791/58099 (2018).
64. 63. Kim YY, Um JH, Yoon JH, Lee DY, Lee YJ, Jee HJ, Kim YM, Jang JS, Chung J, Park HT, Finkel T, Koh H, Yun J . Assessment of mitophagy in mt-Keima Drosophila revealed an essential role of the PINK1-Parkin pathway in in vivo mitophagy induction. FASEB Journal. 2019. Sep;33(9):9742-9751. doi: 10.1096/fj.201900073R.
65. 64. Jeon J, Kwon H, Cho E, Kim KS, Yun J , Lee YC, Kim DH. The effect of coniferaldehyde on neurite outgrowth in neuroblastoma Neuro2a cells. Neurochem Int. 2019 Dec;131:104579. doi: 10.1016/j.neuint.2019.104579.
66. 65. Park JE, Kim YJ, Lee SG, Kim JY, Chung JY, Jeong SY, Koh H, Yun J , Park HT, Yoo YH, Kim JM. Drp1 Phosphorylation Is Indispensable for Steroidogenesis in Leydig Cells. Endocrinology. 2019 Apr 1;160(4):729-743. doi: 10.1210/en.2019-00029.
67. 66. Kim YY, Um JH, Yoon JH, Lee DY, Lee YJ, Kim DH, Park JI, Yun J . p53 regulates mitochondrial dynamics by inhibiting Drp1 translocation into mitochondria during cellular senescence. FASEB Journal . 2020 Feb;34(2):2451-2464.
68. 67. Kim YY, Yoon JH, Um JH, Jeong DJ, Shin DJ, Hong YB, Kim JK, Kim DH, Kim C, Chung CG, Lee SB, Koh H, Yun J . PINK1 alleviates thermal hypersensitivity in a paclitaxel-induced Drosophila model of peripheral neuropathy. PLoS One . 2020 Sep 17;15(9):e0239126.
69. 68. Yi JH, Jeon J, Kwon H, Cho E, Yun J , Lee YC, Ryu JH, Park SJ, Cho JH, Kim DH. Rubrofusarin Attenuates Chronic Restraint Stress-Induced Depressive Symptoms. (2020) Int J Mol Sci . 2020 May 13;21(10):3454. doi: 10.3390/ijms21103454. PMID: 32414166
70. 69. Cai M, Jung I, Kwon H, Cho E, Jeon J, Yun J , Lee YC, Kim DH, Ryu JH. Spinosin Attenuates Alzheimer's Disease-Associated Synaptic Dysfunction via Regulation of Plasmin Activity. (2020) Biomol Ther (Seoul). 2020 Mar 1;28(2):131-136. doi: 10.4062/biomolther.2019.076. PMID: 31791115
71. 70. Cho JH, Lee S, Jeon H, Kim AH, Lee W, Lee Y, Yang S, Yun J , Jung YS, Lee J. Tetrabromobisphenol A-Induced Apoptosis in Neural Stem Cells Through Oxidative Stress and Mitochondrial Dysfunction. Neurotox Res. 2020 Jun;38(1):74-85. doi: 10.1007/s12640-020-00179-z. Epub 2020 Feb 27. PMID: 32108298
72. 71. Kwon H, Cho E, Jeon J, Kim KS, Jin YL, Lee YC, Yun J , Park SJ, Yi JH, Kim DH. Cryptotanshinone enhances neurite outgrowth and memory via extracellular signal-regulated kinase 1/2 signaling. Food Chem Toxicol. 2020 Feb;136:111011. doi: 10.1016/j.fct.2019.111011.
73. 72. Kim YY, Um JH, Shin DJ, Jeong DJ, Hong YB, Yun J . p53-mediated regulation of mitochondrial dynamics plays a pivotal role in the senescence of various normal cells as well as cancer cells. FASEB Journal. 2021 Feb;35(2):e21319. doi: 10.1096/fj.202002007R.
74. 73. Cho YK, Son Y, Saha A, Kim D, Choi C, Kim M, Park JH, Im H, Han J, Kim K, Jung YS, Yun J , Bae EJ, Seong JK, Lee MO, Lee S, Granneman JG, Lee YH. STK3/STK4 signalling in adipocytes regulates mitophagy and energy expenditure. Nat Metab. 2021 Mar;3(3):428-441. doi: 10.1038/s42255-021-00362-2. Epub 2021 Mar 23. PMID: 33758424
75. 74. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Klionsky DJ, et al. Autophagy. 2021 Jan;17(1):1-382. doi: 10.1080/15548627.2020.1797280. Epub 2021 Feb 8. PMID: 33634751
76. 75. Park W, Kim SJ, Cheresh P, Yun J , Lee B, Kamp DW, Kim DH. Magneto mitochondrial dysfunction mediated cancer cell death using intracellular magnetic nano-transducers. Biomater Sci. 2021 Jun 1. doi: 10.1039/d1bm00419k. Online ahead of print. PMID: 34075946
77. 76. Soo-Jin Oh, Byung-Kwan Lim, Jeanho Yun *† and Ok Sarah Shin*†. CVB3-Mediated Q1 Mitophagy Plays an Important Role in Viral Replication via Abrogation of Interferon Pathways. Front. Cell. Infect. Microbiol. 11:704494. doi: 10.3389/fcimb.2021.704494 (*Co-Corresponding authors)
78. 77. Lee JH, Oh SJ, Yun J * and Shin OS* Nonstructural Protein NS1 of Influenza Virus Disrupts Mitochondrial Dynamics and Enhances Mitophagy via ULK1 and BNIP3. Viruses . 2021 Sep 15;13(9):1845. doi: 10.3390/v13091845. (*Co-Corresponding authors)
79. 78. Sonn SK, Song EJ, Seo S, Kim YY, Um JH, Yeo FJ, Lee DS, Jeon S, Lee MN, Jin J, Kweon HY, Kim TK, Kim S, Moon SH, Rhee SG, Chung J, Yang J, Han J, Choi EY, Lee SB, Yun J , Oh GT. Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control. Redox Biol. 2022 Feb 28;51:102275. doi: 10.1016/j.redox.2022.102275.
80. 79. Jang HJ, Kim YY, Lee KM, Shin JE, Yun J . The PINK1 Activator Niclosamide Mitigates Mitochondrial Dysfunction and Thermal Hypersensitivity in a Paclitaxel-Induced Drosophila Model of Peripheral Neuropathy. Biomedicines. 2022 Apr 7;10(4):863. doi: 10.3390/biomedicines10040863.
81. 80. Tran Q, Lee H, Jung JH, Chang SH, Shrestha R, Kong G, Park J, Kim SH, Park KS, Rhee HW, Yun J , Cho MH, Kim KP, Park J. Emerging role of LETM1/GRP78 axis in lung cancer. Cell Death Dis. 2022 Jun 10;13(6):543. doi: 10.1038/s41419-022-04993-5.
82. 81. Han SH, Kim YH, Park SJ, Cho JG, Shin YK, Hong YB, Yun J , Han JY, Park HT, Park JI. COUP-TFII plays a role in cAMP-induced Schwann cell differentiation and in vitro myelination by up-regulating Krox20. J Neurochem. 2023 Jun;165(5):660-681. doi: 10.1111/jnc.15764.
83. 82. Kang KH, Han JE, Kim H, Kim S, Hong YB, Yun J , Nam SH, Choi BO, Koh H. PINK1 and Parkin Ameliorate the Loss of Motor Activity and Mitochondrial Dysfunction Induced by Peripheral Neuropathy-Associated HSPB8 Mutants in Drosophila Models. Biomedicines. 2023 Mar 9;11(3):832. doi: 10.3390/biomedicines11030832.
84. 83. Um JH, Shin DJ, Choi SM, Nathan A, Kim YY, Lee DY, Jeong DJ, Kim DH, Kim K, Kim HY, Nah J, Jeong JH, Yoo E, Shin HK, Park HT, Jo J, Cho JH, Yun J . Selective induction of Rab9-dependent alternative mitophagy using a synthetic derivative of isoquinoline alleviates mitochondrial dysfunction and cognitive deficits in Alzheimer’s disease models. Theranostics . 2024, Jan 1; 14 (1), 56-74. DOI: 10.7150/thno.88718.
85. 84. Oh SJ, Yu JW, Park H, Yun J * and Shin OS* Varicella zoster virus glycoprotein E facilitates PINK1/Parkin-mediated mitophagy to evade STING and MAVS- mediated antiviral innate immunity. Cell Death Dis. 2024 Jan 6;15(1):16. doi: 10.1038/s41419-023-06400-z.. (*Co-Corresponding authors)
86. 85. Lee DY, Lee KM, Um JH, Kim YY, Kim DH, Yun J . The Natural Alkaloid Palmatine Selectively Induces Mitophagy and Restores Mitochondrial Function in an Alzheimer's Disease Mouse Model. Int. J. Mol. Sci . 2023, 24, 16542. https://doi.org/10.3390/ijms242216542
87. 86. Um JH, Lee KM, Kim YY, Lee DY, Kim E, Kim DH, Yun J . Berberine Induces Mitophagy through Adenosine Monophosphate-Activated Protein Kinase and Ameliorates Mitochondrial Dysfunction in PINK1 Knockout Mouse Embryonic Fibroblasts. Int. J. Mol. Sci . 2024, 25, 219. https://doi.org/10.3390/ijms25010219.
88. 87. Kim JE, Park SY, Kwak C, Lee Y, Song DG, Jung JW, Lee H, Shin EA, Pinanga Y, Pyo KH, Lee EH, Kim W, Kim S, Jun CD, Yun J , Choi S, Rhee HW, Liu KH, Lee JW. Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites. Cancer Commun. 2023 Dec 22. doi: 10.1002/cac2.12510.
89. 88. Jeong DJ, Kim YY, Um JH, Shin DJ, Im S, Lee KM, Lee YH, Lim D, Yun J . The Mst1/2-BNIP3 axis is required for mitophagy induction and neuronal viability under mitochondrial stress. Exp Mol Med. 2024 Mar 5. doi: 10.1038/s12276-024-01198-y.
90. 89. Im S, Kim E, Choi JH, Jang HJ, Kim YY, Lee J, Lee YJ, Jeong DJ, Lee KM, Choi D, Yoo EH, Lee HY, Yun J . A novel marine-derived mitophagy inducer ameliorates mitochondrial dysfunction and thermal hypersensitivity in paclitaxel-induced peripheral neuropathy models. Br J Pharmacol. 2024 Jun 26. doi: 10.1111/bph.16476.
91. 90. Oh SJ, Kim YY, Ma R, Choi ST, Choi SM, Cho JH, Yoo Y, Han K, Park H, Yun J * and Shin OS*. Pharmacological targeting of mitophagy via ALT001 improves herpes simplex virus 1-mediated microglial inflammation and promotes amyloid β phagocytosis by restricting HSV1 infection. Theranostics . 2025, March 31; 15(11), 4890-4908. (*Co-Corresponding authors)
92. 91. Im S, Choi SM, Kim YY, Jeong DJ, Um JH, Lee KM, Yoo Y, Cho JH, Yun J A novel isoquinoline mitophagy inducer ameliorates paclitaxel-induced peripheral neuropathy in Drosophila and mouse models. Scientific Reports . 2025 Jul 1;15(1):20960
93. 92. Lee KM, Kim J, Jung HL, Kim YY, Lee J, Lee YJ, Yoo E, Lee HS, Yun J * Exploring mitophagy levels in Drosophila Malpighian tubules unveils the pivotal role of mitophagy in kidney function and diabetic kidney disease. Exp Mol Med . 2025 Oct;57(10):2364-2375.
94. 93. 1. Um JH, Choi SM, Kim YY, Shin DJ, Yoo E, Maeng HJ, Nathan ABP, Jo J, Cho JH, Yun J * Allyl-substituted ALT001 promotes alternative mitophagy and improves therapeutic outcomes in Alzheimer's disease models. Sci Rep. 2026 Apr 17. doi: 10.1038/s41598-026-48974-6.