Mitophagy regulatory pathways including PINK1-parkin signaling and their dysregulation in neurodegenerative diseases

Abstract

What happens when the cell&#39;s own power stations begin to malfunction and accumulate beyond repair? Mitochondrial quality control through selective autophagy, known as mitophagy, represents one of the most important defense systems against cellular damage in post-mitotic neurons. This research examined the molecular mechanisms governing PINK1-Parkin dependent mitophagy and assessed how disruptions in these pathways contribute to Parkinson&#39;s disease (PD), Alzheimer&#39;s disease (AD), and amyotrophic lateral sclerosis (ALS). Using SH-SY5Y neuroblastoma cell lines treated with carbonyl cyanide m-chlorophenylhydrazone (CCCP) to induce mitochondrial depolarization, we measured expression of key mitophagy markers including PINK1, Parkin, p62/SQSTM1, LC3-II, BNIP3L/Nix, and FUNDC1 across control and disease-model conditions. Western blot analysis showed that PINK1 protein levels dropped to 0.38-fold in PD models and 0.71-fold in AD models relative to controls (p < 0.001 and p