Review of PINK1-Parkin-mediated mitochondrial autophagy in Alzheimer's disease

The role of mitophagy in metabolic diseases and its exercise intervention

“…Loganin significantly upregulated postsynaptic density-95 (PSD95), synaptophysin (SYP), Mfn2, and OPA1 protein levels in the hippocampus of 3×Tg-alzheimer disease (AD) mice, downregulated Drp1, Fis1, LC3II, p62, PINK1, Parkin, TOMM20, and COX isoform IV expression, improved amyloid β-protein (Aβ) deposition and synaptic ultrastructure in 3×Tg-AD mice, restored mitochondrial fission/fusion homeostasis, alleviated the abnormal degradation of mitophagy, and restored the learning and memory ability of 3×Tg-AD mice. In vitro experiments further confirmed that Loganin significantly upregulated OPTN expression and downregulated LC3II, p62, PINK1, and Parkin protein expression in Aβ 25-35 -treated human neuroblastoma cells (SK-N-SH), and significantly ameliorated mitochondrial dysfunction, whereas OPTN silencing counteracted the restoration of mitochondrial function by Loganin, confirming that Loganin may improve cognitive function in AD mice by promoting OPTN-mediated mitophagy ( Zhou Y. et al, 2023 ). Melatonin, an endogenous circadian indoleamine secreted by the pineal gland, has a wide range of biological functions, including antioxidant, anti-inflammatory, antitumor, and neuroprotective effects ( Porfirio et al, 2017 ).…”

“…Furthermore, overexpressed circEPS15 could act as a miR-24-3p sponge, inhibit miR-24-3p expression in 1-methyl-4-phenyl pyridine (MPP + )-treated human neuroblastoma cells (SH-SY5Y cells), upregulate the expression of the target gene PINK1, decrease the protein level of SQSTM1/p62, upregulate LC3 expression, and enhance PINK1-Parkin-dependent mitophagy, which subsequently upregulated Bcl-2 and TOMM20 expression, and reduced BAX and Cleaved-Caspase-9 expression, preventing MPP + -induced neuronal damage. In vivo experiments further confirmed that overexpression of circEPS15 significantly inhibited MPTP-induced PD in mice brain tissues with miR-24-3p expression, upregulated PINK1 expression, and enhanced PINK1-Parkin-dependent mitophagy to promote dopaminergic neuronal recovery in PD mice ( Zhou YZ. et al, 2023 ).…”

“…Mitochondria, as determinants of metabolic health, are critical for several physiological processes such as inflammatory responses, OS, immune signal transduction, apoptosis, and stress response ( Harrington et al, 2023 ). Mitochondrial damage and dysfunction are mainly manifested as abnormal ATP supply, increased ROS production, structural changes in mitochondrial cristae, and opening of mitochondrial membrane permeability transition pores, which are key factors leading to the occurrence and development of many metabolic diseases ( Zhou T. et al, 2023 ). To maintain mitochondrial quantity and physiological function, cells can initiate a series of protective mechanisms under stress, including mitochondrial biogenesis, mitochondrial fission/fusion, mitophagy, mitochondrial transport, and others.…”

Insights into the role of mitophagy in lung cancer: current evidence and perspectives

“…In recent years, the elucidation of cellular metabolic pathways’ roles in the progression of lung cancer has garnered increasing attention. In this context, mitophagy, a quintessential process for cellular metabolic regulation and quality assurance, has been recognized as a critical mechanism ( Zhou et al, 2023 ). This specialized autophagic process is indispensable for the removal of impaired or non-functional mitochondria, thereby safeguarding cellular energetic equilibrium and metabolic stability ( Filippelli et al, 2022 ).…”