Functions of outer mitochondrial membrane proteins: mediating the crosstalk between mitochondrial dynamics and mitophagy

Abstract

Most cellular stress responses converge on the mitochondria. Consequently, the mitochondria must rapidly respond to maintain cellular homeostasis and physiological demands by fine-tuning a plethora of mitochondria-associated processes. The outer mitochondrial membrane (OMM) proteins are central to mediating mitochondrial dynamics, coupled with continuous fission and fusion. These OMM proteins also have vital roles in controlling mitochondrial quality and serving as mitophagic receptors for autophagosome enclosure during mitophagy. Mitochondrial fission segregates impaired mitochondria in smaller sizes from the mother mitochondria and may favor mitophagy for eliminating damaged mitochondria. Conversely, mitochondrial fusion mixes dysfunctional mitochondria with healthy ones to repair the damage by diluting the impaired components and consequently prevents mitochondrial clearance via mitophagy. Despite extensive research efforts into deciphering the interplay between fission-fusion and mitophagy, it is still not clear whether mitochondrial fission essentially precedes mitophagy. In this review, we summarize recent breakthroughs concerning OMM research, and dissect the functions of these proteins in mitophagy from their traditional roles in fission-fusion dynamics, in response to distinct context, at the intersection of the OMM platform. These insights into the OMM proteins in mechanistic researches would lead to new aspects of mitochondrial quality control and better understanding of mitochondrial homeostasis intimately tied to pathological impacts.

Nicotine Causes Mitochondrial Dynamics Imbalance and Apoptosis Through ROS Mediated Mitophagy Impairment in Cardiomyocytes

“…Recently, mitophagy was proven to be closely related to mitochondrial dynamics ( Xian and Liou, 2020 ). Short mitochondria induced by mitochondrial fission can be easily targeted and eliminated by mitophagy ( Burman et al, 2017 ; Chen et al, 2016 ; Twig et al, 2008 ; Chen and Dorn, 2013 ).…”

“…Mitochondrial fission is crucial to the initiation of mitophagy, and mitochondrial fusion plays the role of a savior preventing mitophagy ( Twig et al, 2008 ; Twig and Shirihai, 2011 ; Youle and van der Bliek, 2012 ). On the other hand, mitochondrial fusion maintains the quality of mitochondria by diluting the dysfunctional components of mitochondria, which inhibits the progression of mitophagy to some extent ( Xian and Liou, 2020 ). However, the relationship between mitophagy and mitochondrial dynamics is still controversial ( Burman et al, 2017 ; Murakawa et al, 2015 ; Chen et al, 2017 ; Xian and Liou, 2020 ).…”

“…On the other hand, mitochondrial fusion maintains the quality of mitochondria by diluting the dysfunctional components of mitochondria, which inhibits the progression of mitophagy to some extent ( Xian and Liou, 2020 ). However, the relationship between mitophagy and mitochondrial dynamics is still controversial ( Burman et al, 2017 ; Murakawa et al, 2015 ; Chen et al, 2017 ; Xian and Liou, 2020 ). The effects of hindered mitophagic flux on mitochondrial dynamics are largely unknown.…”

The mitochondrial fission factor FIS1 promotes stemness of human lung cancer stem cells via mitophagy

“…After mitochondrial division, senescent and damaged mitochondria are split. Thereafter, the damaged mitochondria are degraded by mitophagy and the excess ROS in the cell is metabolized at the same time [23].…”

ZBTB20 Positively Regulates Oxidative Stress, Mitochondrial Fission, and Inflammatory Responses of ox‐LDL‐Induced Macrophages in Atherosclerosis

“…Mitochondria are well known for their roles in integrating redox, efferocytosis, epigenetic, and apoptotic regulations [56]. How mitochondria function will depend on the shape and density, which are modulated by the fusion/fission balances [57,58]. These functions have been found to be disturbed in macrophages from the AS plaques [59].…”