Mitophagy and Oxidative Stress: The Role of Aging

Abstract

Mitochondrial dysfunction is a hallmark of aging. Dysfunctional mitochondria are recognized and degraded by a selective type of macroautophagy, named mitophagy. One of the main factors contributing to aging is oxidative stress, and one of the early responses to excessive reactive oxygen species (ROS) production is the induction of mitophagy to remove damaged mitochondria. However, mitochondrial damage caused at least in part by chronic oxidative stress can accumulate, and autophagic and mitophagic pathways can become overwhelmed. The imbalance of the delicate equilibrium among mitophagy, ROS production and mitochondrial damage can start, drive, or accelerate the aging process, either in physiological aging, or in pathological age-related conditions, such as Alzheimer’s and Parkinson’s diseases. It remains to be determined which is the prime mover of this imbalance, i.e., whether it is the mitochondrial damage caused by ROS that initiates the dysregulation of mitophagy, thus activating a vicious circle that leads to the reduced ability to remove damaged mitochondria, or an alteration in the regulation of mitophagy leading to the excessive production of ROS by damaged mitochondria.

Oxidative stress-induced impairment of trophoblast function causes preeclampsia through the unfolded protein response pathway

“…The presence of disintegrated mitochondria in the PE placenta may indicate ROS-generated OS and cellular assault thereby disintegrating trophoblast’s intracellular components. OS mediated mitophagy also regulate mitochondrial dysfunction 64 , but recent finding showed a decreased mitophagy in the placentas of PE mice 65 . However, though the causes of mitochondrial dysfunction and mitophagy in PE are still unknown but these chain of events could lead to ER stress, a feat that is well documented in PE 66 – 68 .…”

From Oxidative Stress to Inflammation in the Posterior Ocular Diseases: Diagnosis and Treatment

“…ROS can react rapidly with nitric oxide (NO), generating RNS. These substances are considered as metabolites with a high capacity to oxidize proteins, lipids, and nucleic acids [ 5 ] and enhance autophagy and mitophagy processes [ 6 ], cell dysfunction, necrosis, apoptosis, and cell death [ 7 , 8 ].…”

“…Although the study of these substances focuses on the cellular damage products, they have important cellular functions such as regulators and signaling agents in multiple processes such as apoptosis, mitophagy, adhesion, and cell differentiation [ 6 , 14 , 15 ]. However, when the production of ROS and RNS exceeds the limits of the detoxification system in a prolonged or chronic way, these substances are considered the main mediators of the inflammatory pathology [ 5 , 13 ].…”

Aronia melanocarpa polysaccharide ameliorates inflammation and aging in mice by modulating the AMPK/SIRT1/NF-κB signaling pathway and gut microbiota

“…Importantly, D-Gal-induced brain aging can cause mitochondrial dysfunction and lead to the decline in cognitive ability by inducing inflammatory injury, cell apoptosis, and the reduction of brain-derived neurotrophic factors 20 . Imbalance of the antioxidant defense system plays an important role in the process of aging 21 ; hence, maintaining the maintaining the dynamic balance of redox may be a useful treatment approach to delay D-Gal-induced aging 22 .…”