Mitochondrial Dynamics: A Key Role in Neurodegeneration and a Potential Target for Neurodegenerative Disease

Wang

et al. 2021

Front. Aging Neurosci.

Self Cite

The intracellular energy state will alter under the influence of physiological or pathological stimuli. In response to this change, cells usually mobilize various molecules and their mechanisms to promote the stability of the intracellular energy status. Mitochondria are the main source of ATP. Previous studies have found that the function of mitochondria is impaired in aging, neurodegenerative diseases, and metabolic diseases, and the damaged mitochondria bring lower ATP production, which further worsens the progression of the disease. Silent information regulator-1 (SIRT1) is a multipotent molecule that participates in the regulation of important biological processes in cells, including cellular metabolism, cell senescence, and inflammation. In this review, we mainly discuss that promoting the expression and activity of SIRT1 contributes to alleviating the energy stress produced by physiological and pathological conditions. The review also discusses the mechanism of precise regulation of SIRT1 expression and activity in various dimensions. Finally, according to the characteristics of this mechanism in promoting the recovery of mitochondrial function, the relationship between current pharmacological preparations and aging, neurodegenerative diseases, metabolic diseases, and other diseases was analyzed.

Section: Conclusion and Discussionmentioning

confidence: 76%

Relieving Cellular Energy Stress in Aging, Neurodegenerative, and Metabolic Diseases, SIRT1 as a Therapeutic and Promising Node

Wang

et al. 2021

Front. Aging Neurosci.

Self Cite

“…Dynamic actin along with myoII is required for the proper recruitment of Drp1. Excess actin stabilization, such as what occurs in neurons defective in the actin severing protein Lrrk2, results in Drp1 mis-localization and mitochondrial elongation and may contribute to mitochondrial defects observed in neurodegenerative diseases [221,263]. Disassembly of the actin occurs during mitochondrial fusion allowing mixing of the contents to maintain healthier mitochondria.…”

Section: Mitochondriamentioning

confidence: 99%

“…Preceding the development of tau pathology, changes in actin-dependent processes, including the formation of rods and mis-localization of Drp1, have been observed in neurons in different neurodegenerative disease models [221,263,308,327,328], suggesting that the sequestering of cofilin into cofilin-actin rods could be contributing to defects in many other diseases. We suggest that cofilin dysregulation also might be the initiator of tau pathology.…”

Section: Rods and Tau Pathologymentioning

confidence: 99%

Cofilin and Actin Dynamics: Multiple Modes of Regulation and Their Impacts in Neuronal Development and Degeneration

Bamburg

Minamide

Wiggan

et al. 2021

Cells

Proteins of the actin depolymerizing factor (ADF)/cofilin family are ubiquitous among eukaryotes and are essential regulators of actin dynamics and function. Mammalian neurons express cofilin-1 as the major isoform, but ADF and cofilin-2 are also expressed. All isoforms bind preferentially and cooperatively along ADP-subunits in F-actin, affecting the filament helical rotation, and when either alone or when enhanced by other proteins, promotes filament severing and subunit turnover. Although self-regulating cofilin-mediated actin dynamics can drive motility without post-translational regulation, cells utilize many mechanisms to locally control cofilin, including cooperation/competition with other proteins. Newly identified post-translational modifications function with or are independent from the well-established phosphorylation of serine 3 and provide unexplored avenues for isoform specific regulation. Cofilin modulates actin transport and function in the nucleus as well as actin organization associated with mitochondrial fission and mitophagy. Under neuronal stress conditions, cofilin-saturated F-actin fragments can undergo oxidative cross-linking and bundle together to form cofilin-actin rods. Rods form in abundance within neurons around brain ischemic lesions and can be rapidly induced in neurites of most hippocampal and cortical neurons through energy depletion or glutamate-induced excitotoxicity. In ~20% of rodent hippocampal neurons, rods form more slowly in a receptor-mediated process triggered by factors intimately connected to disease-related dementias, e.g., amyloid-β in Alzheimer’s disease. This rod-inducing pathway requires a cellular prion protein, NADPH oxidase, and G-protein coupled receptors, e.g., CXCR4 and CCR5. Here, we will review many aspects of cofilin regulation and its contribution to synaptic loss and pathology of neurodegenerative diseases.

“…Mitochondrial hyper fission leads to mitochondrial fragmentation and damage, decreased mitochondrial membrane potential, increased permeability, and decreased ATP production. At the same time, the disruption of mitochondrial autophagy leads to an excessive accumulation of intracellular mitochondria with abnormal function and high levels of oxygen radical production, producing large amounts of neurotoxic substances and eventually causing neurodegeneration disease (Portz and Lee, 2021;Yang et al, 2021). Parkinson's disease, Alzheimer's disease, and Huntington's chorea, several neurodegenerative diseases are associated with mitochondrial dysfunction (Stanga et al, 2020; Table 2).…”

Section: Changes In Mitochondrial Dynamics Related Diseases Mitochondrial Dynamics and Neurodegenerative Diseasesmentioning

confidence: 99%

Molecular Machinery and Pathophysiology of Mitochondrial Dynamics

Chiu

Kuo

2021

Front. Cell Dev. Biol.

Mitochondria are double-membraned organelles that exhibit fluidity. They are the main site of cellular aerobic respiration, providing energy for cell proliferation, migration, and survival; hence, they are called “powerhouses.” Mitochondria play an important role in biological processes such as cell death, cell senescence, autophagy, lipid synthesis, calcium homeostasis, and iron balance. Fission and fusion are active processes that require many specialized proteins, including mechanical enzymes that physically alter mitochondrial membranes, and interface proteins that regulate the interaction of these mechanical proteins with organelles. This review discusses the molecular mechanisms of mitochondrial fusion, fission, and physiopathology, emphasizing the biological significance of mitochondrial morphology and dynamics. In particular, the regulatory mechanisms of mitochondria-related genes and proteins in animal cells are discussed, as well as research trends in mitochondrial dynamics, providing a theoretical reference for future mitochondrial research.