Mitophagy in Health and Disease


Mitochondria, the indispensable and highly dynamic, energy-generating organelles in all eukaryotic cells, play essential roles in fundamental cellular processes, including calcium buffering, reactive oxygen species generation, ion homeostasis, lipid metabolism, cellular differentiation, cell death and apoptosis among others. Given the fact that mitochondria are the main sites of high metabolic activity and, hence, a hotspot of metabolic stress, it is not surprising that the impairment of their function is involved in the development and progression of a broad spectrum of pathological conditions. Thus, several and redundant quality control mechanisms have evolved to sustain and restore mitochondrial function, including mitochondrial biogenesis, dynamics, mitochondrial derived vesicles, proteasome system and mitochondrial unfolded protein response. Excessive mitochondrial damage triggers the removal of the entire organelle via mitochondria selective autophagy, known as mitophagy. Mitophagy is a highly regulated cellular process, and the major degradation pathway by which cells regulate mitochondrial population and fitness in response to their metabolic state.

Research in mitophagy has exploded over the last decade unraveling that mitophagy is a complex, multi-step and multi-factorial cellular process. A diverse repertoire of mitophagy-related proteins has been revealed highlighting an intricate regulatory network of mitochondrial quality control systems that respond differentially to developmental, hormonal and/or environmental signals. Several molecular mechanisms have been identified to mediate mitochondrial removal in a cell type- and tissue-dependent manner. Moreover, the complex interplay between mitophagy signalling pathways ensures energy metabolism, which is critical for tissue and organ homeostasis. Indeed, defective mitophagy results in accrual of dysfunctional mitochondria leading to energetic stress, elevated ROS levels and unresolved inflammation that is accompanied by cellular and tissue degeneration. Thus, mitophagy has a pivotal role in cellular function, tissue integrity and, subsequently, in influencing organismal development, health-span and survival.

The delineation of the molecular underpinnings and the identification of novel pharmacological interventions that modulate mitophagy and mitochondrial function is at the forefront of research. Several synthetic and natural occurring compounds, such as nicotinamide mononucleotide, spermidine and urolithin A, have demonstrated the ability to protect against age-associated pathologies by mediating the elimination of impaired mitochondria, thereby, sustaining energy homeostasis and cellular function.

The aim of the current Research Topic is to outline and review the key questions that still remain regarding the molecular and physiological basis of mitophagy, highlighting the most recent discoveries and challenges in the field. Areas to be covered in the current Research Topic may include, but are not limited to:
- Molecular mechanisms of mitophagy regulation;
- Pharmacological modulators of mitochondrial removal;
- Mitophagy in metabolism and ageing;
- Mitophagy in physiological and pathological conditions;
- Methods to assess mitophagy in vivo and in vitro.


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Sana George

Managing Editor

Journal of Health and Medical Research

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