A time to reap, a time to sow: Mitophagy and biogenesis in cardiac pathophysiology

Abstract

Balancing mitophagy and mitochondrial biogenesis is essential for maintaining a healthy population of mitochondria and cellular homeostasis. Coordinated interplay between these two forces that govern mitochondrial turnover plays an important role as an adaptive response against various cellular stresses that can compromise cell survival. Failure to maintain the critical balance between mitophagy and mitochondrial biogenesis or homeostatic turnover of mitochondria results in a population of dysfunctional mitochondria that contribute to various disease processes. In this review we outline the mechanics and relationships between mitophagy and mitochondrial biogenesis, and discuss the implications of a disrupted balance between these two forces, with an emphasis on cardiac physiology.

Signalling mechanisms underlying doxorubicin and Nox2 NADPH oxidase‐induced cardiomyopathy: involvement of mitofusin‐2

“…In fact, there was tendency towards reduced cell viability in all three measures, which included two of membrane integrity (live cell protease assay – AFC, Janus Green Whole Cell) and also mitochondrial activity (MTT). It appears, therefore, that in an environment associated with extreme loss of Mfn2 activity, HL‐1 cardiomyocytes are more likely to undergo necrotic transformation; it is also possible that impairment of autophagic processes will impact on mitochondrial quality control (Andres et al, 2015). As further information emerges, it seems that there is equivalent evidence that maintained levels of Mfn2 may be required to counteract cell oxidative stress; for example, further to ROS induced by hypoxia/reoxygenation in cardiomyocytes, up‐regulated Mfn2 expression prevented imbalance in mitochondrial dynamics (Dong et al, 2016).…”

Mitochondrial quality control: Easy come, easy go

“…Impaired mitochondrial quality control results in accumulation of damaged mitochondria that may release more reactive oxygen species [8], produce less ATP [9], have a lower threshold for cytochrome c release resulting in apoptosis [10], undergo mitochondrial permeability transition pore (MPTP) opening resulting in necrosis [11], or may release mitochondrial components (mtHSP60, oxidized mitochondrial DNA) into cytosol where its recognition by receptors for damage-associated molecular patterns (DAMP) activates inflammation [12]. Mitochondrial turnover is therefore an integral aspect of quality control in which dysfunctional mitochondria are selectively eliminated through autophagy (mitophagy) and replaced through expansion of preexisting mitochondria (biogenesis) [13]. In this review, we focus on the mechanics of mitochondrial turnover and the techniques currently employed to measure and monitor the dynamic network, constantly kept in balance by two arms of mitochondrial quality control: mitophagy and mitochondrial biogenesis.…”

Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes

“…In the current obesity/diabetes epidemic caffeine metabolism is possibly defective [18] and effects of caffeine is via Sirt 1/p53 regulated mitochondria biogenesis with caffeine doses related to p53 mediated mitophagy relevant to cellular programmed cell death [17]. Sirt 1 is relevant to mitophagy [17][18][19][20] in myocardial infarction [81][82][83][84][85][86] and hepatic caffeine metabolism now important to endothelial death and interference of the endothelial NO synthase Figure 3) in the plasma and secondary caffeine saturation of cell membranes. Caffeine can be converted to theophylline in cells but beneficial theophylline effects may be sensitive to toxic elevated caffeine levels in cells.…”