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. 2023;21(5):1026-1041.
doi: 10.2174/1570159X21666230314140528.

Pharmacological Progress of Mitophagy Regulation

Sheikh Arslan Sehgal  1   2 , Hao Wu  3 , Muhammad Sajid  4 , Summar Sohail  5 , Muhammad Ahsan  6 , Gulnaz Parveen  7 , Mehreen Riaz  7 , Muhammad Saleem Khan  8 , Muhammad Nasir Iqbal  1 , Abbeha Malik  1
Affiliations

Pharmacological Progress of Mitophagy Regulation

Sheikh Arslan Sehgal et al. Curr Neuropharmacol. 2023.

Abstract

With the advancement in novel drug discovery, biologically active compounds are considered pharmacological tools to understand complex biological mechanisms and the identification of potent therapeutic agents. Mitochondria boast a central role in different integral biological processes and mitochondrial dysfunction is associated with multiple pathologies. It is, therefore, prudent to target mitochondrial quality control mechanisms by using pharmacological approaches. However, there is a scarcity of biologically active molecules, which can interact with mitochondria directly. Currently, the chemical compounds used to induce mitophagy include oligomycin and antimycin A for impaired respiration and acute dissipation of mitochondrial membrane potential by using CCCP/FCCP, the mitochondrial uncouplers. These chemical probes alter the homeostasis of the mitochondria and limit our understanding of the energy regulatory mechanisms. Efforts are underway to find molecules that can bring about selective removal of defective mitochondria without compromising normal mitochondrial respiration. In this report, we have tried to summarize and status of the recently reported modulators of mitophagy.

Keywords: Mitophagy; mitochondria; mitochondrial quality control; neurological disorders; pharmacology; power management system.

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Conflict of interest statement

The authors declare no conflict of interest, financial or otherwise.

Figures

Fig. (1)
Fig. (1)
Mitophagy mechanism independent from PINK1-parkin (A) the process of mitophagy mediated through the accumulation of BNIP3 and NIX on mitochondria (B) Cardiolipin on the surface of the mitochondria triggers a mitophagic response (C) PGAM5 coordination with FUNDC1 leads to recruit the autophagosomes through LC3 (D) Mitophagy induction through BNIP3.
Fig. (2)
Fig. (2)
Mitophagy induction models (A) The mechanism of iron chelators to complete the autophagic mitochondrial removal (B) Unknown ubiquitin mechanism (C) the induction of mitophagy through PMI promotes the autophagosomal targeting of mitochondria for disposal (D) ubiquitinating the proteins of mitochondria to provide more ubiquitin substrate.
Fig. (3)
Fig. (3)
Ub-dependent mitophagy activation through PINK1–parkin modulator pathway. The mitophagy pathway of PINK1-parkin can be altered through pharmacological approaches (A) the utilization of pifithrin-a (small-molecule p53 inhibitor) made a pharmacological intervention to restore the clearance of mitochondria (B) a cell-permeable precursor, the increase of PINK1 kinase activity enhances the recruitment of parkin and mitochondrial phosphorylation.
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