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The PINK1/Parkin pathway is essential for preventing cellular stress and is particularly implicated in mitochondrial quality control. Dysregulation of this pathway is associated with certain neurodegenerative disorders (i.e. Parkinson's Disease), emphasizing its significance in cellular health.
- PINK1 = PTEN-induced putative kinase 1
Parkin is a E3 ubiquitin ligase, which means it adds ubiquitin molecules to target proteins
New research as shown that mitophagy in SARC-CoV-2-infected cells is activated via the PINK1/Parkin pathway (Shang et al., 2022).
Regarding fluorosis, a new study by Hu et al (2024) has demonstrated that fluoride-induced bone injury is also mediated via via PINK1/Parkin pathway (Hu et al., 2024).
Recent research in heart, liver, and lung has shown that PINK1/Parkin-mediated mitophagy is regulated by thyroid hormone [TH] (Bi et al., 2019; Chi et al., 2017; Singh et al., 2018; Yu et al., 2018; Zhang et al., 2021).
The role of Gq/11 in mitophagy has been discussed in numerous recent reviews (Navarro-Lérida et al., 2022; Sánchez-Fernández et al., 2016).
COVID-19
Shang C, Liu Z, Zhu Y, Lu J, Ge C, Zhang C, Li N, Jin N, Li Y, Tian M, Li X - "SARS-CoV-2 Causes Mitochondrial Dysfunction and Mitophagy Impairment" Front Microbiol 12:780768 (2022). doi: 10.3389/fmicb.2021.780768
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8770829/
"Mitophagy Is Activated via Pink1/Parkin Pathway in SARS-CoV-2-Infected Cells."
Fluoride
Hu Y, Li Y, Li M, Zhao T, Zhang W, Wang Y, He Y, Zhao H, Li H, Wang T, Zhao Y, Wang J, Wang J - "Calcium supplementation attenuates fluoride-induced bone injury via PINK1/Parkin-mediated mitophagy and mitochondrial apoptosis in mice" J Hazard Mater 465:133411 (2024) doi: 10.1016/j.jhazmat.2023.133411
"Fluoride can activate bone mitophagy through the PINK1/Parkin pathway."
Gq/11
Navarro-Lérida I, Aragay AM, Asensio A, Ribas C - "Gq Signaling in Autophagy Control: Between Chemical and Mechanical Cues" Antioxidants (Basel). 11(8):1599 (2022). doi: 10.3390/antiox11081599
https://www.mdpi.com/2076-3921/11/8/1599
Sánchez-Fernández G, Cabezudo S, García-Hoz C, Benincá C, Aragay AM, Mayor F Jr, Ribas C - "Gαq signalling: the new and the old" Cell Signal 26(5):833-48 (2014). doi: 10.1016/j.cellsig.2014.01.010
https://www.sciencedirect.com/science/a ... 6814000217
Thyroid Hormone
Bi W, Jia J, Pang R, Nie C, Han J, Ding Z, Liu B, Sheng R, Xu J, Zhang J - "Thyroid hormone postconditioning protects hearts from ischemia/reperfusion through reinforcing mitophagy" Biomed Pharmacother 118:109220 (2019). doi: 10.1016/j.biopha.2019.109220.
"Meanwhile, we found that THPostC [T3 postconditioning] stimulated PINK1/Parkin pathway, a critical regulator for mitophagy."
Chi HC, Chen SL, Lin SL, Tsai CY, Chuang WY, Lin YH, Huang YH, Tsai MM, Yeh CT, Lin KH - "Thyroid hormone protects hepatocytes from HBx-induced carcinogenesis by enhancing mitochondrial turnover" Oncogene 36(37):5274-5284 (2017). doi: 10.1038/onc.2017.136.
https://www.nature.com/articles/onc2017136
"Using microarray data analysis, this protective effect of TH [Thyroid Hormone] was found to be mediated via activation of PTEN-induced kinase 1 (PINK1) in hepatocytes. PINK1, in turn, activated and recruited Parkin, an E3 ligase, to ubiquitinate MITO-associated HBx protein and trigger selective mitophagy. The pathological significance of the TH/PINK1 pathway in liver protection was confirmed by the concomitant decrease in expression of both TR and PINK1 in matched HCC tumor tissues and negatively correlated with aggressive progression of cancer and poor prognosis. Our data indicate that TH/PINK1/Parkin pathway has a critical role in protecting hepatocytes from HBx-induced carcinogenesis."
Singh BK, Sinha RA, Tripathi M, Mendoza A, Ohba K, Sy JAC, Xie SY, Zhou J, Ho JP, Chang CY, Wu Y, Giguère V, Bay BH, Vanacker JM, Ghosh S, Gauthier K, Hollenberg AN, McDonnell DP, Yen PM - "Thyroid hormone receptor and ERRα coordinately regulate mitochondrial fission, mitophagy, biogenesis, and function" Sci Signal 11(536):eaam5855 (2018). doi: 10.1126/scisignal.aam5855
https://pubmed.ncbi.nlm.nih.gov/29945885/
"TH induced the expression of genes regulating mitochondrial fission (Drp1) and mitophagy (Pink1 and Parkin)...in mouse livers."
Yu G, Tzouvelekis A, Wang R, Herazo-Maya JD, Ibarra GH, Srivastava A, de Castro JPW, DeIuliis G, Ahangari F, Woolard T, Aurelien N, Arrojo EDR, Gan Y, Graham M, Liu X, Homer RJ, Scanlan TS, Mannam P, Lee PJ, Herzog EL, Bianco AC, Kaminski N - "Thyroid hormone inhibits lung fibrosis in mice by improving epithelial mitochondrial function" Nat Med 24:39–49 (2018)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5760280/
Zhang Y, Yu G, Kaminski N, Lee PJ - "PINK1 mediates the protective effects of thyroid hormone T3 in hyperoxia-induced lung injury" Am J Physiol Lung Cell Mol Physiol 320(6):L1118-L1125 (2021) doi: 10.1152/ajplung.00598.2020
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285622/