Mitophagy in Atherosclerosis: from Mechanism to Therapy

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2023 Jun 1

PMID 37261351

Authors

Yanhong Zhang

Jiajun Weng

Luyao Huan

Song Sheng

Fengqin Xu

Affiliations

Soon will be listed here.

Abstract

Mitophagy is a type of autophagy that can selectively eliminate damaged and depolarized mitochondria to maintain mitochondrial activity and cellular homeostasis. Several pathways have been found to participate in different steps of mitophagy. Mitophagy plays a significant role in the homeostasis and physiological function of vascular endothelial cells, vascular smooth muscle cells, and macrophages, and is involved in the development of atherosclerosis (AS). At present, many medications and natural chemicals have been shown to alter mitophagy and slow the progression of AS. This review serves as an introduction to the field of mitophagy for researchers interested in targeting this pathway as part of a potential AS management strategy.

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References

Ma S, Chen J, Feng J, Zhang R, Fan M, Han D . Melatonin Ameliorates the Progression of Atherosclerosis via Mitophagy Activation and NLRP3 Inflammasome Inhibition. Oxid Med Cell Longev. 2018; 2018:9286458. PMC: 6142770. DOI: 10.1155/2018/9286458. View

Akabane S, Uno M, Tani N, Shimazaki S, Ebara N, Kato H . PKA Regulates PINK1 Stability and Parkin Recruitment to Damaged Mitochondria through Phosphorylation of MIC60. Mol Cell. 2016; 62(3):371-384. DOI: 10.1016/j.molcel.2016.03.037. View

Wang X, Zhang J, Xiu C, Yang J, Fang J, Lei Y . Ginseng-Sanqi-Chuanxiong (GSC) Extracts Ameliorate Diabetes-Induced Endothelial Cell Senescence through Regulating Mitophagy via the AMPK Pathway. Oxid Med Cell Longev. 2020; 2020:7151946. PMC: 7495226. DOI: 10.1155/2020/7151946. View

Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J . NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016; 164(5):896-910. PMC: 4769378. DOI: 10.1016/j.cell.2015.12.057. View

Ma W, Sun X, Wang Y, Zhu Y, Han X, Liu N . Restoring mitochondrial biogenesis with metformin attenuates β-GP-induced phenotypic transformation of VSMCs into an osteogenic phenotype via inhibition of PDK4/oxidative stress-mediated apoptosis. Mol Cell Endocrinol. 2018; 479:39-53. DOI: 10.1016/j.mce.2018.08.012. View

Crozet P, Margalha L, Confraria A, Rodrigues A, Martinho C, Adamo M . Mechanisms of regulation of SNF1/AMPK/SnRK1 protein kinases. Front Plant Sci. 2014; 5:190. PMC: 4033248. DOI: 10.3389/fpls.2014.00190. View

Byun K, Oh S, Yang J, Lee S, Son K, Byun K . Ecklonia cava extracts decrease hypertension-related vascular calcification by modulating PGC-1α and SOD2. Biomed Pharmacother. 2022; 153:113283. DOI: 10.1016/j.biopha.2022.113283. View

Pradhan P, Vijayan V, Gueler F, Immenschuh S . Interplay of Heme with Macrophages in Homeostasis and Inflammation. Int J Mol Sci. 2020; 21(3). PMC: 7036926. DOI: 10.3390/ijms21030740. View

Popelka H, Klionsky D . Multiple structural rearrangements mediated by high-plasticity regions in Atg3 are key for efficient conjugation of Atg8 to PE during autophagy. Autophagy. 2021; 17(8):1805-1808. PMC: 8386745. DOI: 10.1080/15548627.2021.1954457. View

10.

Jeon S . Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016; 48(7):e245. PMC: 4973318. DOI: 10.1038/emm.2016.81. View

11.

Wu W, Tian W, Hu Z, Chen G, Huang L, Li W . ULK1 translocates to mitochondria and phosphorylates FUNDC1 to regulate mitophagy. EMBO Rep. 2014; 15(5):566-75. PMC: 4210082. DOI: 10.1002/embr.201438501. View

12.

Liu Y, Li J, Han Y, Chen Y, Liu L, Lang J . Advanced glycation end-products suppress autophagy by AMPK/mTOR signaling pathway to promote vascular calcification. Mol Cell Biochem. 2020; 471(1-2):91-100. DOI: 10.1007/s11010-020-03769-9. View

13.

Docherty C, Carswell A, Friel E, Mercer J . Impaired mitochondrial respiration in human carotid plaque atherosclerosis: A potential role for Pink1 in vascular smooth muscle cell energetics. Atherosclerosis. 2017; 268:1-11. PMC: 6565844. DOI: 10.1016/j.atherosclerosis.2017.11.009. View

14.

Nascimbeni A, Giordano F, Dupont N, Grasso D, Vaccaro M, Codogno P . ER-plasma membrane contact sites contribute to autophagosome biogenesis by regulation of local PI3P synthesis. EMBO J. 2017; 36(14):2018-2033. PMC: 5509996. DOI: 10.15252/embj.201797006. View

15.

Orsi A, Razi M, Dooley H, Robinson D, Weston A, Collinson L . Dynamic and transient interactions of Atg9 with autophagosomes, but not membrane integration, are required for autophagy. Mol Biol Cell. 2012; 23(10):1860-73. PMC: 3350551. DOI: 10.1091/mbc.E11-09-0746. View

16.

Poellinger L, Johnson R . HIF-1 and hypoxic response: the plot thickens. Curr Opin Genet Dev. 2004; 14(1):81-5. DOI: 10.1016/j.gde.2003.12.006. View

17.

Xi J, Rong Y, Zhao Z, Huang Y, Wang P, Luan H . Scutellarin ameliorates high glucose-induced vascular endothelial cells injury by activating PINK1/Parkin-mediated mitophagy. J Ethnopharmacol. 2021; 271:113855. DOI: 10.1016/j.jep.2021.113855. View

18.

Chang X, Zhang T, Liu D, Meng Q, Yan P, Luo D . Puerarin Attenuates LPS-Induced Inflammatory Responses and Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells through Mitochondrial Quality Control. Oxid Med Cell Longev. 2021; 2021:6659240. PMC: 7937474. DOI: 10.1155/2021/6659240. View

19.

Pi X, Xie L, Patterson C . Emerging Roles of Vascular Endothelium in Metabolic Homeostasis. Circ Res. 2018; 123(4):477-494. PMC: 6205216. DOI: 10.1161/CIRCRESAHA.118.313237. View

20.

Wang Y, Zhang X, Chen W, Gao L, Li J, Song T . Cortistatin ameliorates Ang II-induced proliferation of vascular smooth muscle cells by inhibiting autophagy through SSTR3 and SSTR5. Life Sci. 2020; 253:117726. DOI: 10.1016/j.lfs.2020.117726. View