Impaired mitochondrial energy metabolism

Abstract

Abstract For a system to perform efficiently under any circumstance, it requires a huge energy source for proper functioning and yield. Mitochondrial oxidative phosphorylation (OXPHOS) plays a key role in meeting the cellular energetic demands. Neurodegenerative diseases (NDs) are the consequence of multifactorial complications and have a high-risk predisposition with growing age; therefore, impaired mitochondrial metabolism can play a key role in exaggerating such syndromes. Here, we comprehensively elaborate on the intrinsic and extrinsic mechanisms involved in impaired OXPHOS and the evidence and implications of impaired OXPHOS in age-related NDs such as Alzheimer s disease, Parkinson s disease, Huntington s disease, and amyotrophic lateral sclerosis (AD, PD, HD, and ALS). OXPHOS is predisposed to a large number of intrinsic factors of the cell (e.g., mutations, calcium imbalance, intracellular reactive oxygen species) as well as environmental exposures (e.g., mitochondrial toxins, uncouplers, drugs, pollutants, and diet). Impaired OXPHOS could increase the susceptibility to NDs through oxidative stress, inducing mutations, limiting the energy transferred to the neurons and deposition of fats leading to plaque accumulation. Therefore, with increasing age, a decrease in the mitochondrial oxidative metabolism because of host and environmental exposures might confer susceptibility to develop a ND, such as AD, PD, HD, and ALS. Such effects including impaired mitochondrial bioenergetics and dysfunction are now considered etiopathogenic signatures of ND.