Citation:

Cardiovascular Research Supplements ( 2016 ) 111 ( S1 ), S57

Objective: Mitophagy is a critical cellular process that selectively targets damaged mitochondria for autophagosomal degradation both under baseline conditions and in response to stress to prevent oxidative damage and cell death. Recent studies have linked dysfunctional mitochondria function and reduced autophagy with the development of age-related pathologies. However, the significance of mitochondrial autophagy in vessel wall in response to atherogenic lipid stressors is not known. We aimed to investigate the role of mitophagy on human vascular smooth muscle cells (VSMC) apoptosis induced by oxidized low-density lipoproteins (LDL).

Methods and Results: Using a variety of complementary techniques, we reported for the first time that the engulfment of defective mitochondria by autophagosomes occured in human VSMC in response to oxidized LDL. The molecular mechanism mediating mitophagy in human VSMC involved Drp1-mediated mitochondrial fission, accumulation of PTEN-induced putative kinase 1 (PINK1) and the recruitment of the E3 ubiquitin ligase Parkin to the mitochondria. Likewise, we found increased mitochondrial proteins ubiquitination and LC3 association. Using flow cytometry assay, we showed that PINK1 and Parkin silencing impaired mitophagy flux and enhanced oxidized LDL-induced human VSMC apoptosis although overexpressed PINK1 and Parkin were protective by limiting cell death. Moreover, reduced Bax levels found in human VSMC-overexpressing Parkin indicated cross talk among mitophagy and mitochondrial apoptotic signalling pathways.

Conclusions: Altogether these data demonstrate that mitophagy is a safeguard mechanism against human VSMC apoptosis induced by atherogenic stressors and highlight mitophagy as a potential target to stabilize atherosclerotic plaque.

Mitophagy acts as a safeguard mechanism against human vascular smooth muscle cell apoptosis induced by atherogenic lipids

Abstract

About the speaker

Doctor Cecile Vindis

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Poster session 2 - Cell death and apoptosis - Vascular

The Event

Frontiers in CardioVascular Biology 2016