Mitophagy pathways in health and disease

Abstract

Mitophagy is an evolutionarily conserved process involving the autophagic targeting and clearance of mitochondria destined for removal. Recent insights into the complex nature of the overlapping pathways regulating mitophagy illustrate mitophagy’s essential role in maintaining the health of the mitochondrial network. In this review, we highlight recent studies that have changed the way mitophagy is understood, from initiation through lysosomal degradation. We outline the numerous mitophagic receptors and triggers, with a focus on basal and physiologically relevant cues, offering insight into why they lead to mitochondrial removal. We also explore how mitophagy maintains mitochondrial homeostasis at the organ and system levels and how a loss of mitophagy may play a role in a diverse group of diseases, including cardiovascular, metabolic, and neurodegenerative diseases. With disrupted mitophagy affecting such a wide array of physiological processes, a deeper understanding of how to modulate mitophagy could provide avenues for numerous therapies.

Fermented Soy Products: Beneficial Potential in Neurodegenerative Diseases

“…In contrast, these effects were reversed by pre-treatment with soy isoflavones, suggesting that the compounds can restore the autophagy function of dopaminergic neurons in the substantia nigra. In fact, the dysregulation of autophagy is emerging as a major etiology of PD as reported by a number of studies [ 92 , 98 , 99 , 100 ]. In particular, restoring mitochondria-specific autophagy (termed mitophagy) in PD neurons has been demonstrated to prevent oxidative stress and dopaminergic neuronal damage in in vivo models and in patient-derived cells [ 98 , 101 , 102 , 103 ].…”

Modulation of Autophagy: A Novel “Rejuvenation” Strategy for the Aging Liver

“…Similar to the above, mitophagy is the process of selective degradation for damaged or redundant mitochondria via macroautophagy [ 61 , 62 ]. Mitophagy plays a crucial role in mitochondrial quality control and regeneration [ 63 , 64 ].…”

The Mitochondrial Proteome of Tumor Cells: A SnapShot on Methodological Approaches and New Biomarkers

“…Mitochondrial dynamics is also strictly intertwined with mitophagy, the specific autophagic disruption of mitochondria [ 35 , 36 ]. The mitochondrial genome is highly exposed to ROS, being mitochondria the main sites of ROS production through the respiratory chain.…”

“…This results in the accumulation of mtDNA mutations that can impair the mitochondrial functionality and, thus, the cell survival. The activation of mitophagy occurs when mitochondria are damaged beyond the ability of other quality control pathways or when the cell has to remove superfluous mitochondria to meet metabolic or developmental needs in response to a plethora of stimuli and triggers [ 35 , 37 ]. Two pathways regulate mitophagy: the phosphatase and tensin homologue (PTEN)-induced putative kinase 1 (PINK1)-PARKIN pathway and the PARKIN-independent pathway.…”

“…Mitochondrial fission plays a crucial role in mitophagy as it is preceded by division of mitochondria. Fragmented mitochondria are then incapsulated by the autophagosomes [ 35 ]. Accordingly, the overexpression of OMM transmembrane receptors for DRP1 triggers mitophagy [ 38 ].…”