Mitochondrial dynamics in neurological diseases: a narrative review

Shen, Ya; Wen-li, Jiang; Li, Xin; Cao, Axiu; Li, Dan; Li, Shangze; Yang, Jing; Qian, J.

doi:10.21037/atm-22-2401

Cited by 3 publications

(2 citation statements)

References 96 publications

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“…The outer mitochondrial membrane (OMM) mitofusins, MFN1 and MFN2, required for fusion of the OMM, while the inner mitochondrial membrane (IMM) protein optic atrophy-1, OPA1, is responsible for fusion of the IMM. Fission occurs in response to cell division and stress conditions and requires the translocation of the dynamin-related protein 1, DRP1, to the OMM, where it divides the mitochondria into two [ 9 , 75 ]. Two distinct fusion events have been described: complete fusion and partial fusion [ 76 ].…”

Section: Parkin Regulates Mitochondrial Dynamicsmentioning

confidence: 99%

PRKN-linked familial Parkinson’s disease: cellular and molecular mechanisms of disease-linked variants

Clausen,

Okarmus,

Voutsinos

et al. 2024

Cell. Mol. Life Sci.

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Parkinson’s disease (PD) is a common and incurable neurodegenerative disorder that arises from the loss of dopaminergic neurons in the substantia nigra and is mainly characterized by progressive loss of motor function. Monogenic familial PD is associated with highly penetrant variants in specific genes, notably the PRKN gene, where homozygous or compound heterozygous loss-of-function variants predominate. PRKN encodes Parkin, an E3 ubiquitin-protein ligase important for protein ubiquitination and mitophagy of damaged mitochondria. Accordingly, Parkin plays a central role in mitochondrial quality control but is itself also subject to a strict protein quality control system that rapidly eliminates certain disease-linked Parkin variants. Here, we summarize the cellular and molecular functions of Parkin, highlighting the various mechanisms by which PRKN gene variants result in loss-of-function. We emphasize the importance of high-throughput assays and computational tools for the clinical classification of PRKN gene variants and how detailed insights into the pathogenic mechanisms of PRKN gene variants may impact the development of personalized therapeutics.

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Section: Parkin Regulates Mitochondrial Dynamicsmentioning

confidence: 99%

PRKN-linked familial Parkinson’s disease: cellular and molecular mechanisms of disease-linked variants

Clausen,

Okarmus,

Voutsinos

et al. 2024

Cell. Mol. Life Sci.

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“…Similarly, in HD, abnormal DRP1 activation contributes to mitochondrial fragmentation and dysfunction, leading to neuronal degeneration [49]. Studies have shown that inhibiting the fission machinery through DRP1 or FIS1 knockdown results in the accumulation of oxidized mitochondrial proteins, reduced respiration, and impaired insulin secretion, which are associated with the progression of neurodegenerative diseases [60,[90][91][92][93].…”

Section: Protein Machinery In Mitochondrial Fissionmentioning

confidence: 99%

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

Grel,

Woznica,

Ratajczak

et al. 2023

IJMS

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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.

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Impact of Epstein–Barr Virus Nuclear Antigen 1 on Neuroinflammation in PARK2 Knockout Mice

Cossu,

Tomizawa,

Noda

et al. 2024

IJMS

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This study aimed to explore the intricate relationship between mitochondrial dysfunction, infection, and neuroinflammation, focusing specifically on the impact of pathogenic epitopes of the Epstein–Barr Virus (EBV) nuclear antigen 1 (EBNA1) in a mouse model of mitochondrial dysfunctions. The investigation included female middle-aged PARK2−/− and C57BL/6J wild-type mice immunized with EBNA1386–405 or with active experimental autoimmune encephalomyelitis (EAE) induction by the myelin oligodendrocyte glycoprotein (MOG)35–55 peptide. The PARK2−/− mice developed more severe EAE than the wild-type mice. Following immunization with EBNA1386–405, only PARK2−/− exhibited symptoms resembling EAE. During the acute phase, PARK2−/− mice immunized with either MOG35–55 or EBNA1386–405 exhibited a similar infiltration of the T cells and macrophages in the spinal cord and decreased glial fibrillary acidic protein (GFAP) expression in the brain. However, the EBNA1386–405 -immunized PARK2−/− mice showed significantly increased frequencies of CD8a+ T cells and CD11c+ B cells, and distinct cytokine profiles in the periphery compared to the wild-type controls. These findings highlight the role of EBV in exacerbating inflammation, particularly in the context of mitochondrial deficiencies.

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Mitochondrial dynamics in neurological diseases: a narrative review

Cited by 3 publications

References 96 publications

PRKN-linked familial Parkinson’s disease: cellular and molecular mechanisms of disease-linked variants

PRKN-linked familial Parkinson’s disease: cellular and molecular mechanisms of disease-linked variants

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

Impact of Epstein–Barr Virus Nuclear Antigen 1 on Neuroinflammation in PARK2 Knockout Mice

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