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Review
. 2022 Jun 17:9:917135.
doi: 10.3389/fcvm.2022.917135. eCollection 2022.

Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease

Jianguo Lin  1   2 , Jinlong Duan  1 , Qingqing Wang  1 , Siyu Xu  1   3 , Simin Zhou  1 , Kuiwu Yao  1   4
Affiliations
Review

Mitochondrial Dynamics and Mitophagy in Cardiometabolic Disease

Jianguo Lin et al. Front Cardiovasc Med. .

Abstract

Mitochondria play a key role in cellular metabolism. Mitochondrial dynamics (fusion and fission) and mitophagy, are critical to mitochondrial function. Fusion allows organelles to share metabolites, proteins, and mitochondrial DNA, promoting complementarity between damaged mitochondria. Fission increases the number of mitochondria to ensure that they are passed on to their offspring during mitosis. Mitophagy is a process of selective removal of excess or damaged mitochondria that helps improve energy metabolism. Cardiometabolic disease is characterized by mitochondrial dysfunction, high production of reactive oxygen species, increased inflammatory response, and low levels of ATP. Cardiometabolic disease is closely related to mitochondrial dynamics and mitophagy. This paper reviewed the mechanisms of mitochondrial dynamics and mitophagy (focus on MFN1, MFN2, OPA1, DRP1, and PINK1 proteins) and their roles in diabetic cardiomyopathy, myocardial infarction, cardiac hypertrophy, heart failure, atherosclerosis, and obesity.

Keywords: cardiometabolic disease; diabetic cardiomyopathy; mitochondrial dynamics; mitochondrial fission; mitochondrial fusion; mitophagy; myocardial infarction.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Mitochondrial structure and function. Mitochondria can be divided into four functional regions from outside to inside: outer mitochondrial membrane, intermembrane space, inner mitochondrial membrane, and mitochondrial matrix. Mitochondria can regulate metabolism, signal transduction, immune regulation, cell senescence, and death through TCA cycle metabolites, cytochrome c (Cytc), mtDNA, Ca2+, ROS, AMPK, and other factors, thus affecting the balance of the human body.
Figure 2
Figure 2
Mitochondrial function. (A) Mitochondrial fusion is mediated by homo-and heterotypic interactions between MFN1 and MFN2 at the OMM and OPA1 at the IMM. (B) DRP1 binds to its receptors at the OMM at sites of contact with the ER. (C) The PINK1/Parkin-dependent pathway: under stress conditions, PINK1 was stable on OMM, which promoted the recruitment of Parkin. Parkin ubiquitizes several outer membrane components. The polyubiquitin chain is then phosphorylated by PINK1 as a “eat me” signal for the autophagy mechanism. Autophagy receptors (AR) recognize phosphorylated polyubiquitin chains on mitochondrial proteins and initiate autophagosome formation by binding to LC3. (D) The PINK1/Parkin-independent pathway: mitophagy receptors, such as BNIP3, NIX, FKBP8, and FUNDC1 are located to directly interact with OMM and LC3 to mediate mitochondrial clearance. (E) Mitochondria are engulfed by autophagosomes, which fuse with lysosomes and catabolize them.
Figure 3
Figure 3
Mechanisms of mitochondrial dynamics and mitophagy in cardiometabolic diseases.
See this image and copyright information in PMC

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