Abstract
Mitochondria are known as highly dynamic organelles essential for energy production. Intriguingly, in the recent years, mitochondria have revealed the ability to maintain cell homeostasis and ultimately regulate cell fate. This regulation is achieved by evoking mitochondrial quality control pathways that are capable of sensing the overall status of the cellular environment. In a first instance, actions to maintain a robust pool of mitochondria take place; however, if unsuccessful, measures that lead to overall cell death occur. One of the central key players of these mitochondrial quality control pathways is PINK1 (PTEN-induce putative kinase), a mitochondrial targeted kinase. PINK1 is known to interact with several substrates to regulate mitochondrial functions, and not only is responsible for triggering mitochondrial clearance via mitophagy, but also participates in maintenance of mitochondrial functions and homeostasis, under healthy conditions. Moreover, PINK1 has been associated with the familial form of Parkinson’s disease (PD). Growing evidence has strongly linked mitochondrial homeostasis to the central nervous system (CNS), a system that is replenished with high energy demanding long-lasting neuronal cells. Moreover, sporadic cases of PD have also revealed mitochondrial impairments. Thus, one could speculate that mitochondrial homeostasis is the common denominator in these two forms of the disease, and PINK1 may play a central role in maintaining mitochondrial homeostasis. In this review, we will discuss the role of PINK1 in the mitochondrial physiology and scrutinize its role in the cascade of PD pathology.
Highlights
Mitochondria are essential for life; they play an intimate role in almost all aspects of cellular function, since they are responsible for calcium intracellular homeostasis, metabolite biosynthesis, cell proliferation, differentiation and apoptosis, and, their most known purpose, energy production
Studies using mito-QC, a tandem mCherry-GFP tag fused to a mitochondrial targeting sequence, showed that basal mitophagy is readily detectable and abundant in many tissues of PINK1 deficient flies [117]. These findings provide evidence that, at least in these experimental conditions, PINK1 and parkin are not essential for basal mitophagy in Drosophila, further underpinning that the molecular mechanisms of basal mitophagy remain largely obscure
Almost 20 years after PINK1 was linked to this disease a lot of research has characterized this protein and its mutations associated to Parkinson’s disease (PD)
Summary
Mitochondria are essential for life; they play an intimate role in almost all aspects of cellular function, since they are responsible for calcium intracellular homeostasis, metabolite biosynthesis, cell proliferation, differentiation and apoptosis, and, their most known purpose, energy production. This close interaction between mitochondria and the cell is the main reason why mitochondrial dysregulation is one of the underlying causes of several pathologies, such as cancer, neurological diseases and metabolic disorders. Mitochondria are highly dynamic organelles that evoke several mechanisms to respond to bioenergetic challenges, such as biogenesis, events of fusion/fission and mitophagy, a pathway that controls their overall fate
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