Evolving Concepts of Mitochondrial Dynamics

Abstract

The concept that mitochondria are highly dynamic is as widely accepted as it is untrue for a number of important contexts. Healthy mitochondria of the most energy-dependent and mitochondrial-rich mammalian organ, the heart, only rarely undergo fusion or fission and are seemingly static within cardiac myocytes. Here, we revisit mitochondrial dynamism with a fresh perspective developed from the recently discovered multifunctionality of mitochondrial fusion proteins and newly defined mechanisms for direct cross talk between mitochondrial dynamics, biogenesis, quality control, and trafficking pathways. Insights gained from comparing static mitochondrial biology in cardiac myocytes and dynamic mitochondrial biology in neurons are reviewed with the goal of understanding contextual fallacies of overly generalized characterizations of these essential and intriguing organelles.

The impact of DRP1 on myocardial fibrosis in the obese minipig

“…In the mouse heart in vivo, interrupting mitochondrial fission or fusion, types of dynamic impairment causes cardiac damage that is lethal approximately 8 weeks after intervention . These studies support major pathophysiological importance of functional interactions between mitochondrial fission/fusion and mitochondrial quality control pathways with evidence in vivo …”

“…7 These studies support major pathophysiological importance of functional interactions between mitochondrial fission/fusion and mitochondrial quality control pathways with evidence in vivo. 8 Prolonged severe obesity may result in left ventricular (LV) dilation, increased LV wall stress, compensatory LV hypertrophy, myocardial fibrosis and LV diastolic dysfunction with progression to systolic dysfunction if wall stress remains high. 9,10 The high-fat diet (HFD) is known to be a major cause of obesity, and the HFD is used to induce cardiometabolic dysfunction and for investigation of the mechanisms responsible for metabolic heart disease.…”

Melatonin attenuates myocardial ischemia‐reperfusion injury via improving mitochondrial fusion/mitophagy and activating the AMPK‐OPA1 signaling pathways

“…Functionally, several of the cardiomyocyte biological processes affected by mitochondrial homeostasis, including apoptosis, metabolic reprogramming, contractile, and autophagy, are tightly linked to mitochondrial fission/fusion, which suggests that changes in the mitochondrial morphology may underlie many of the phenotypes that preserve cardiomyocyte viability. Normal mitochondrial fission promotes the mitochondrial redistribution, while fusion maintains a healthy mitochondrial network . However, aberrant mitochondrial fission has been considered a prerequisite for cardiomyocyte intrinsic apoptosis initiation at the stage of I/R injury by inducing damage to mitochondrial DNA copy/transcription, interrupting mitochondrial bioenergetics, and triggering the caspase‐9‐dependent death pathway .…”

“…Normal mitochondrial fission promotes the mitochondrial redistribution, while fusion maintains a healthy mitochondrial network. 47,48 However, aberrant mitochondrial fission has been considered a prerequisite for cardiomyocyte intrinsic apoptosis initiation at the stage of I/R injury by inducing damage to mitochondrial DNA copy/transcription, 49 interrupting mitochondrial bioenergetics, and triggering the caspase-9-dependent death pathway. 50 The accumulation of abnormal mitochondria can damage neighboring normal mitochondria by propagating injurious signals and inducing widespread mPTP opening and mitochondrial malfunction.…”

Mitochondrial Dysfunction in Age‐Related Metabolic Disorders

“…[ 79,81 ] Pink1 mediated phosphorylation of MFN2 turns this fusion protein into a mitophagy receptor. [ 82 ] Although it is evident that PINK1 and Parkin are critical for mitophagy, loss of functional mutations of these proteins are implicated in age‐related neurodegenerative diseases such as Parkinson's disease. While mitophagy can be triggered through Pink1/Parkin‐mediated pathway, it can also be mediated by mitophagy receptors such as autophagy‐related gene 32 (ATG32), [ 83,84 ] BNIP3‐like (NIX/BNIP3L), [ 85 ] BCL2 and adenovirus E1B 19‐kDa‐interacting protein (BNIP3), [ 86 ] and fun14 domain‐containing protein 1 (FUNDC1).…”