Mitophagy in Cardiovascular Diseases

Abstract

Cardiovascular diseases are one of the leading causes of death. Increasing evidence has shown that pharmacological or genetic targeting of mitochondria can ameliorate each stage of these pathologies, which are strongly associated with mitochondrial dysfunction. Removal of inefficient and dysfunctional mitochondria through the process of mitophagy has been reported to be essential for meeting the energetic requirements and maintaining the biochemical homeostasis of cells. This process is useful for counteracting the negative phenotypic changes that occur during cardiovascular diseases, and understanding the molecular players involved might be crucial for the development of potential therapies. Here, we summarize the current knowledge on mitophagy (and autophagy) mechanisms in the context of heart disease with an important focus on atherosclerosis, ischemic heart disease, cardiomyopathies, heart failure, hypertension, arrhythmia, congenital heart disease and peripheral vascular disease. We aim to provide a complete background on the mechanisms of action of this mitochondrial quality control process in cardiology and in cardiac surgery by also reviewing studies on the use of known compounds able to modulate mitophagy for cardioprotective purposes.

The Mitochondrial Outer Membrane Protein Tom70-Mediator in Protein Traffic, Membrane Contact Sites and Innate Immunity

“…Aberrant mitochondria are removed by a selective form of autophagy, termed mitophagy, which is a crucial mechanism in mitochondrial quality control [ 206 ]. Dysfunctional mitochondria and impaired mitophagy are observed in many pathological conditions and the mechanisms and implications of mitophagy were investigated in molecular detail particularly with respect to Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Alzheimer’s disease (AD) [ 207 , 208 , 209 ].…”

Sirtuin 3 governs autophagy‐dependent glycolysis during Angiotensin II‐induced endothelial‐to‐mesenchymal transition

“…1 Evidence suggests that defective autophagy in endothelial cells (ECs) contributes to endothelial dysfunction, which is involved in the pathological process of vascular diseases. 2,3 Systemic-or endothelial-specific deletion of core autophagy-regulated genes (ATG), including ATG3, ATG5, and ATG7, in mice attenuates nitric oxide (NO) generation and ischemia-related angiogenesis while accelerating the endothelial-to-mesenchymal transition (EndoMT). [4][5][6] Loss of Beclin 1-induced endothelium senescence.…”

Mitochondrial Pathobiology and Metabolic Remodeling in Progression to Overt Systolic Heart Failure

“…At the initial stage of remodeling, such as at compensated hypertrophy, mitophagy may play a cardioprotective role by maintaining mitochondrial quality control. However, with the advancement of cardiac remodeling and activation of signaling pathways that induce mitochondrial dysfunction and apoptosis, the mitophagy system becomes overwhelmingly saturated and insufficient to maintain a healthy mitochondrial population [16,17]. This is supported by the observation that the mitochondria in HFrEF are at a relatively advanced stage of vacuolar degeneration compared to a normal or phenylephrine-stressed adult cardiac myocyte for 2 h, and HFpEF, Figure 3A-C.…”

“…Moreover, within the areas of clustered mitochondria, often numerous lysosomes are observed fusing with the surrounding mitochondria pointing towards active mitophagy [12,14], Figure 1B. Molecular markers of autophagy and mitophagy are upregulated early on in compensated pathological hypertrophy or HFpEF, and intensify with the progression to HFrEF [9,12,16]. At the initial stage of remodeling, such as at compensated hypertrophy, mitophagy may play a cardioprotective role by maintaining mitochondrial quality control.…”