Abstract
Mitochondria are highly dynamic organelles that are important for many diverse cellular processes, such as energy metabolism, calcium buffering, and apoptosis. Mitochondrial biology and dysfunction have recently been linked to different types of cancers and neurodegenerative diseases, most notably Parkinson's disease. Thus, a better understanding of the quality control systems that maintain a healthy mitochondrial network can facilitate the development of effective treatments for these diseases. In this perspective, we will discuss recent advances on two mitochondrial quality control pathways: the UPS and mitophagy, highlight how new players may be contributing to regulate these pathways. We believe the proteases involved will be key and novel regulators of mitochondrial quality control, and this knowledge will provide insights into future studies aimed to combat neurodegenerative diseases.
Highlights
Mitochondrial Quality Control SystemsParkinson’s disease (PD) is a neurodegenerative disease of the central nervous system that results from the loss of dopaminergic neurons in the substantia nigra (SN) region of the brain
The form that is of interest to us and the field of mitochondrial dynamics and quality control is a selective type of macroautophagy, called mitophagy, which mediates the removal of damaged mitochondria that can be toxic to the cell [17, 18]
Impairment of mitochondrial quality control, such as mitophagy, has been recently proposed to be one of the mechanisms that trigger the neurodegenerative process [4]. These findings suggest that common mechanisms may underlie both familial and sporadic forms of PD, and impaired mitochondrial clearance could be one such mechanism
Summary
Parkinson’s disease (PD) is a neurodegenerative disease of the central nervous system that results from the loss of dopaminergic neurons in the substantia nigra (SN) region of the brain. Mitochondria are vital for many diverse processes in the cell, such as energy metabolism, calcium buffering, and cell apoptosis These double-membrane-bound organelles are often called the “powerhouses” of the cell because they generate the cell’s supply of energy in the form of ATP. The form that is of interest to us and the field of mitochondrial dynamics and quality control is a selective type of macroautophagy, called mitophagy, which mediates the removal of damaged mitochondria that can be toxic to the cell [17, 18]. The initial step in mitophagy entails recruiting double-membrane-bound vesicles called autophagosomes [19] These structures first engulf mitochondria and the surrounding cytosolic constituents and subsequently fuse with the lysosome, which degrades the sequestered cargo [16]. A better understanding of the systems at play and their relationship with mitochondrial metabolism and intrinsic proapoptotic events may lead to the development of novel screening tools and therapeutic treatments for several debilitating neurodegenerative human diseases like PD
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