Mitophagy and Neuroinflammation: A Compelling Interplay

Abstract

Mitochondria are the main sites of energy production and a major source of metabolic stress. Not surprisingly, impairment of mitochondrial homeostasis is tightly associated with the development and progression of a broad spectrum of human pathologies, including neurodegenerative disorders. Mitophagy mediates the selective degradation of damaged organelles, thus promoting cellular viability and tissue integrity. Defective mitophagy triggers cellular senescence and prolonged neuroinflammation, leading eventually to cell death and brain homeostasis collapse. Here, we survey the intricate interplay between mitophagy and neuroinflammation, highlighting that mitophagy can be a focal point for therapeutic interventions to tackle neurodegeneration.

Mitochondria in Aging and Alzheimer’s Disease: Focus on Mitophagy

“…As Aβ aggregation and hyperphosphorylation of τ lead to excessive reactive oxygen species production, interaction with mitochondrial proteins leads to AD pathology and may accelerate impaired mitophagy observed in AD. Therefore, mitochondrial defects are the signatures of AD and tauopathy because the most crucial energy-producing organelle was impaired in interfering with abnormal proteins like with Aβ and p-τ (Charmpilas and others 2022; Fang and others 2019). This triggers the damaged and dysfunctional mitochondria, accumulation, which is closely related to mitophagy impairments in AD and tauopathies.…”

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases

“…Mitophagy is involved in the clearance of damaged mitochondria and the alleviation of the hyper-reactive neuroinflammation ( Charmpilas et al, 2022 ). In AD, the accumulation of Aβ plaques and hyperphosphorylated tau increases and mitophagy processes decrease, thus enhancing neuroinflammation ( Lautrup et al, 2019 ).…”