Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective

Xu, Sutong; Zhang, Xi; Liu, Chenming; Liu, Qiulu; Chai, Huazhen; Luo, Yuan; Li, Siguang

doi:10.3389/fcell.2021.688789

Cited by 17 publications

(12 citation statements)

References 164 publications

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“…Epigenetic alterations are the main mechanisms in development and tumorigenesis. Mitochondria, as the main energy supplier, play a pivotal role in the regulation of epigenetics [ 54 ].…”

Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

“…The TCA intermediate metabolites in mitochondria such as acetyl-CoA and NAD + regulate the nuclear epigenome as the substrate of acetylation and a cofactor of deacetylation, respectively [ 54 , 162 ]. Other co-factors, including flavin adenine dinucleotide (FAD) and α-KG are closely associated with the above process, and the biosynthesis of the metabolic coenzymes depends on intracellular ATP levels and mitochondrial function [ 20 , 163 , 164 ].…”

Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

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An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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Mitochondria are not only the main energy supplier but are also the cell metabolic center regulating multiple key metaborates that play pivotal roles in epigenetics regulation. These metabolites include acetyl-CoA, α-ketoglutarate (α-KG), S-adenosyl methionine (SAM), NAD+, and O-linked beta-N-acetylglucosamine (O-GlcNAc), which are the main substrates for DNA methylation and histone post-translation modifications, essential for gene transcriptional regulation and cell fate determination. Tumorigenesis is attributed to many factors, including gene mutations and tumor microenvironment. Mitochondria and epigenetics play essential roles in tumor initiation, evolution, metastasis, and recurrence. Targeting mitochondrial metabolism and epigenetics are promising therapeutic strategies for tumor treatment. In this review, we summarize the roles of mitochondria in key metabolites required for epigenetics modification and in cell fate regulation and discuss the current strategy in cancer therapies via targeting epigenetic modifiers and related enzymes in metabolic regulation. This review is an important contribution to the understanding of the current metabolic-epigenetic-tumorigenesis concept.

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“…Epigenetic alterations are the main mechanisms in development and tumorigenesis. Mitochondria, as the main energy supplier, play a pivotal role in the regulation of epigenetics [ 54 ].…”

Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

Section: Mitochondria Function In Epigenetic Regulationmentioning

confidence: 99%

An Epigenetic Role of Mitochondria in Cancer

Liu

Chen

Wang

et al. 2022

Cells

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“…We have previously described that mice lacking Rnd3 expression show defects in the development of the CNS ( Mocholi et al, 2011 ; Ballester-Lurbe et al, 2015 ; Kaur et al, 2020 ; Madrigal et al, 2021 ). We now describe some subcellular phenotypes, such as increased content of lipid droplets and accumulation of mitochondria with irregular morphology, that might be compatible with defects in autophagy or mitophagy, as those described in neurodegenerative diseases like Alzheimer’s, Parkinson’s, Huntington’s diseases and amyotrophic lateral sclerosis ( Xu et al, 2021 ). Biogenesis and fusion of membranes are required in autophagy, and regulators of the actin cytoskeleton dynamics have been shown to be involved in this process ( Kast and Dominguez, 2017 ).…”

Section: Discussionmentioning

confidence: 78%

“…Neurodegenerative diseases are complex entities characterized by a gradual loss of neuronal function. In some of these diseases, including Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s Disease (HD) and Amyotrophic Lateral Sclerosis (ALS), common pathological features are the accumulation of aggregate-prone proteins that causes neuronal degeneration ( Menzies et al, 2017 ) and an imbalance of mitochondrial homeostasis characterized by decreased activity of respiratory chain enzymes and abnormal morphology ( Xu et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

Cueto-Ureña

Mocholí

Escrivá-Fernández

et al. 2022

Front. Cell Dev. Biol.

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Autophagy is a highly conserved process that mediates the targeting and degradation of intracellular components to lysosomes, contributing to the maintenance of cellular homeostasis and to obtaining energy, which ensures viability under stress conditions. Therefore, autophagy defects are common to different neurodegenerative disorders. Rnd3 belongs to the family of Rho GTPases, involved in the regulation of actin cytoskeleton dynamics and important in the modulation of cellular processes such as migration and proliferation. Murine models have shown that Rnd3 is relevant for the correct development and function of the Central Nervous System and lack of its expression produces several motor alterations and neural development impairment. However, little is known about the molecular events through which Rnd3 produces these phenotypes. Interestingly we have observed that Rnd3 deficiency correlates with the appearance of autophagy impairment profiles and irregular mitochondria. In this work, we have explored the impact of Rnd3 loss of expression in mitochondrial function and autophagy, using a Rnd3 KO CRISPR cell model. Rnd3 deficient cells show no alterations in autophagy and mitochondria turnover is not impaired. However, Rnd3 KO cells have an altered mitochondria oxidative metabolism, resembling the effect caused by oxidative stress. In fact, lack of Rnd3 expression makes these cells strictly dependent on glycolysis to obtain energy. Altogether, our results demonstrate that Rnd3 is relevant to maintain mitochondria function, suggesting a possible relationship with neurodegenerative diseases.

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“…Mitochondria are multifunctional subcellular organelles that are essential for numerous cellular functions, including generation of cellular energy, intracellular Ca 2+ homeostasis, ROS production, and activation of intrinsic cell death pathways [ 34 – 36 ]. Mitochondrial dysfunction has been implicated in a series of diverse diseases including PD and has been reported to be a central event in PD pathogenesis [ 37 ]. Activation of p53-mediated mitochondrial apoptotic changes and the subsequent cell death of dopaminergic neurons have been underlined in neurodegeneration [ 38 ].…”

Section: P53 With Mitochondriamentioning

confidence: 99%

Association of p53 with Neurodegeneration in Parkinson’s Disease

Luo

Sun

Wang

et al. 2022

Parkinson's Disease

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p53 is a vital transcriptional protein implicated in regulating diverse cellular processes, including cell cycle arrest, DNA repair, mitochondrial metabolism, redox homeostasis, autophagy, senescence, and apoptosis. Recent studies have revealed that p53 levels and activity are substantially increased in affected neurons in cellular and animal models of Parkinson’s disease (PD) as well as in the brains of PD patients. p53 activation in response to neurodegenerative stress is closely associated with the degeneration of dopaminergic neurons accompanied by mitochondrial dysfunction, reactive oxygen species (ROS) production, abnormal protein aggregation, and impairment of autophagy, and these pathogenic events have been implicated in the pathogenesis of PD. Pathogenic p53 integrates diverse cellular stresses and activate these downstream events to induce the degeneration of dopaminergic neurons; thus, it plays a crucial role in the pathogenesis of PD and appears to be a potential target for the treatment of the disease. We reviewed the current knowledge concerning p53-dependent neurodegeneration to better understand the underlying mechanisms and provide possible strategies for PD treatment by targeting p53.

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Role of Mitochondria in Neurodegenerative Diseases: From an Epigenetic Perspective

Cited by 17 publications

References 164 publications

An Epigenetic Role of Mitochondria in Cancer

An Epigenetic Role of Mitochondria in Cancer

Rnd3 Expression is Necessary to Maintain Mitochondrial Homeostasis but Dispensable for Autophagy

Association of p53 with Neurodegeneration in Parkinson’s Disease

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