The emerging multifaceted role of PINK1 in cancer biology

Abstract

For its various important functions in cells, phosphatase and tensin homolog‐induced kinase 1 (PINK1) has drawn considerable attention for the role it plays in early‐onset Parkinson's disease. In recent years, emerging evidence has supported the hypothesis that PINK1 plays a part in regulating many physiological and pathophysiological processes in cancer cells, including cytoplasmic homeostasis, cell survival, and cell death. According to the findings of these studies, PINK1 can function as a tumor promoter or suppressor, showing a duality that is dependent on the context. In this study we review the mechanistic characters relating to PINK1 based on available published data from peer‐reviewed articles, The Cancer Genome Atlas data mining, and cell‐based assays. This mini review focuses on some of the interplays between PINK1 and the context and recent developments in the field, including its growing involvement in mitophagy and its nonmitophagy organelles‐related function. This review aims to help readers better grasp how PINK1 is functioning in cell physiological and pathophysiological processes, especially in cancer biology.

GPD1L inhibits renal cell carcinoma progression by regulating PINK1/Parkin‐mediated mitophagy

“…Mitophagy, a highly regulated multistep procedure of selective removal of dysfunctional or damaged mitochondria, is crucial for maintaining the metabolic balance of mitochondrial homeostasis in the process of cell development, 17 However, excessive mitophagy can lead to mitochondrial dysfunction, bioenergetic deficits and subsequent cell death 18 . A growing number of studies have documented that the PINK1/Parkin pathway plays a crucial role in the progression of tumorigenesis 19,20 . The results from clinical cohorts showed that PINK1 was significantly positively correlated with patients and may serve as an independent predictor for overall survival in kidney cancer 21 .…”

“… 18 A growing number of studies have documented that the PINK1/Parkin pathway plays a crucial role in the progression of tumorigenesis. 19 , 20 The results from clinical cohorts showed that PINK1 was significantly positively correlated with patients and may serve as an independent predictor for overall survival in kidney cancer. 21 In addition, PINK1 could suppress the growth and invasion of cells, while loss of PINK1 resulted in the Warburg effect by promoting the elevation of hypoxia‐inducible factor‐1 and reactive oxygen species in glioblastoma.…”

Mortalin: Protein partners, biological impacts, pathological roles, and therapeutic opportunities

“…To rescue loss of mortalin phenotypes, Parkin and PINK1 increase lysosomal-mediated mitochondrial clearance and facilitate autophagic machinery ( Burbulla et al, 2014 ). The current evidence indicates that PINK1 can function as either a pro- or an anti-tumorigenic protein in different tumors, showing a duality dependent on context ( Wang et al, 2022 ). PINK1 regulates cell survival, stress resistance, mitochondrial homeostasis, and the cell cycle, all of which are key signaling pathways misused by cancer cells during tumor initiation and progression.…”

Identification and structural characterization of small molecule inhibitors of PINK1

“…Thus, while the molecular mechanism of PINK1 activation by MTK458 remains unclear, these assays demonstrate the usefulness of chemical probes in dissecting the molecular mechanisms of drugs and the robustness of PRT062607 as an inhibitor of PINK1. Finally, high PINK1 levels are associated with poorer prognosis in some cancers such as breast cancers, and thus PINK1 inhibition may prove beneficial for the treatment of those tumors 53 .…”