Mitochondrial Dynamics in Neurodegenerative Diseases: Unraveling the Role of Fusion and Fission Processes

Abstract

Neurodegenerative diseases (NDs) are a diverse group of disorders characterized by the progressive degeneration and death of neurons, leading to a range of neurological symptoms. Despite the heterogeneity of these conditions, a common denominator is the implication of mitochondrial dysfunction in their pathogenesis. Mitochondria play a crucial role in creating biomolecules, providing energy through adenosine triphosphate (ATP) generated by oxidative phosphorylation (OXPHOS), and producing reactive oxygen species (ROS). When they’re not functioning correctly, becoming fragmented and losing their membrane potential, they contribute to these diseases. In this review, we explore how mitochondria fuse and undergo fission, especially in the context of NDs. We discuss the genetic and protein mutations linked to these diseases and how they impact mitochondrial dynamics. We also look at the key regulatory proteins in fusion (MFN1, MFN2, and OPA1) and fission (DRP1 and FIS1), including their post-translational modifications. Furthermore, we highlight potential drugs that can influence mitochondrial dynamics. By unpacking these complex processes, we aim to direct research towards treatments that can improve life quality for people with these challenging conditions.

Knockdown of PTEN Disrupts PINK1/Parkin-mediated Mitophagy and Promotes Hippocampal Neuronal Cell Death Following Experimental Status Epilepticus

“…Neurodegenerative diseases, such as Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), and Multiple Sclerosis (MS), are age-related chronic wasting diseases characterized by neurodegenerative changes (Grel et al 2023). Although these neurodegenerative diseases differ in pathogenic events, onset, and progression, the presence of dysfunctional mitochondria are common features (Rodolfo et al 2018).…”

Post-Acute Sequelae And Mitochondrial Aberration In SARS-CoV-2 Infection

“…Instead, pathological disturbances resulting in damage to mitochondrial components have the potential to affect the whole mitochondrial compartment, while individual components of the mitochondrial compartment are degraded and recycled as necessary. Mitochondrial fusion-fission processes have been found to be disrupted in several diseases, including neurodegeneration, obesity, type II diabetes, and COVID-19 [75,76]. Disruption in mitochondrial dynamics can cause oxidative stress, mitochondrial disfunction and dysregulation of the innate immune response during infection by SARS-CoV-2.…”

Nicotine aggravates pancreatic fibrosis in mice with chronic pancreatitis via mitochondrial calcium uniporter

“…They regulate cell biology by maintaining the balance of ROS and calcium homeostasis [10][11][12] . Numerous studies have indicated a strong correlation between mitochondrial dysfunction and the development of various diseases [13][14][15] . Therefore, investigating mitochondrial function may provide new insights for the treatment of CP.…”