Emerging role of mitophagy in human diseases and physiology

Abstract

Mitophagy is a process of selective removal of damaged or unnecessary mitochondria using autophagic machinery. Mitophagy plays an essential role in maintaining mitochondrial quality control and homeostasis. Mitochondrial dysfunctions and defective mitophagy in neurodegenerative diseases, cancer, and metabolic diseases indicate a close link between human disease and mitophagy. Furthermore, recent studies showing the involvement of mitophagy in differentiation and development, suggest that mitophagy may play a more active role in controlling cellular functions. A better understanding of mitophagy will provide insights about human disease and offer novel chance for treatment. This review mainly focuses on the recent implications for mitophagy in human diseases and normal physiology.

Assessment of mitophagy in mt‐Keima Drosophila revealed an essential role of the PINK1‐Parkin pathway in mitophagy induction in vivo

“…Recent studies have found that mitophagy levels change during the differentiation of various types of human cells (32,34,47). Although the requirement for mitophagy in the differentiation process has to be further proved, programmed mitophagy has been proposed to play an active role in the process of cell differentiation and reprogramming through remodeling the cellular mitochondrial pool (6,10). Consistent with the notion that mitophagy plays a role in mitochondrial remodeling, we observed significant increases in the level of mitophagy in the latter stages of embryogenesis, which are a period of tissue and organ formation.…”

“…Subsequent studies further ABBREVIATIONS: da, daughterless; L3, third instar; mt-Keima, mitochondria-targeted fluorescent protein Keima; NH 4 Cl, ammonium chloride; PINK1, phosphatase and tensin homolog-induced putative kinase 1; RNAi, RNA interference; UAS, upstream activation sequence revealed that mitophagy plays an important role in various aspects of normal physiology. Recent studies have also suggested that deregulated mitophagy activity is closely associated with various human diseases beyond neurodegenerative diseases, including cancer, liver, and cardiovascular diseases (10).…”

Keratin 6a mutations lead to impaired mitochondrial quality control

“…Elimination of old or dysfunctional mitochondria via autophagy is called mitophagy. Disturbed mitophagy and autophagy lead to a number of human diseases such as cardiomyopathies, and neurodegenerative and skin diseases . Functional autophagy is especially important in terminal differentiation of keratinocytes, which lose their organelles during the course of keratinization to become dead corneocytes in the outermost epidermal layer.…”

Inhibition of mitochondrial autophagy protects donor lungs for lung transplantation against ischaemia‐reperfusion injury in rats via the mTOR pathway

“…10,11 In addition, mitochondrial autophagy not only plays a role in cell survival, but also affects cell death. 13 With this aforementioned dual role, mitochondrial autophagy is also involved in the pathogenesis of various diseases, including cancer, heart disease, neurodegeneration and infections. 13 With this aforementioned dual role, mitochondrial autophagy is also involved in the pathogenesis of various diseases, including cancer, heart disease, neurodegeneration and infections.…”

“…12 Moreover, a recent study manifested the role of mitochondrial autophagy in the maintenance of mitochondrial homeostasis and quality control, cellular development and differentiation. 13 With this aforementioned dual role, mitochondrial autophagy is also involved in the pathogenesis of various diseases, including cancer, heart disease, neurodegeneration and infections. 14 For instance, selective mitochondrial autophagy in conjunction with macroautophagy alleviates the ability of chondrogenesis in adipose stem cells (ASCs) of equine metabolic syndrome (EMS).…”