Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns

Jetto, Cuckoo Teresa; Nambiar, Akshaya; Manjithaya, Ravi

doi:10.3389/fcell.2022.837337

Cited by 23 publications

(22 citation statements)

References 284 publications

(295 reference statements)

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“…• Golgiphagy. Recently, a new type of autophagy has been discovered, Golgiphagy [ 71 , 72 , 73 , 74 ], which modulates the amount of Golgi membranes. According to Rahman et al (2022) [ 75 ], Golgiphagy is a selective type of autophagy that regulates Golgi Complex Turnover.…”

Section: Autophagymentioning

confidence: 99%

Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Gómez-Virgilio

Silva-Lucero

Flores-Morelos

et al. 2022

Cells

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Autophagy is a highly conserved lysosomal degradation pathway active at basal levels in all cells. However, under stress conditions, such as a lack of nutrients or trophic factors, it works as a survival mechanism that allows the generation of metabolic precursors for the proper functioning of the cells until the nutrients are available. Neurons, as post-mitotic cells, depend largely on autophagy to maintain cell homeostasis to get rid of damaged and/or old organelles and misfolded or aggregated proteins. Therefore, the dysfunction of this process contributes to the pathologies of many human diseases. Furthermore, autophagy is highly active during differentiation and development. In this review, we describe the current knowledge of the different pathways, molecular mechanisms, factors that induce it, and the regulation of mammalian autophagy. We also discuss its relevant role in development and disease. Finally, here we summarize several investigations demonstrating that autophagic abnormalities have been considered the underlying reasons for many human diseases, including liver disease, cardiovascular, cerebrovascular diseases, neurodegenerative diseases, neoplastic diseases, cancers, and, more recently, infectious diseases, such as SARS-CoV-2 caused COVID-19 disease.

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Section: Autophagymentioning

confidence: 99%

Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Gómez-Virgilio

Silva-Lucero

Flores-Morelos

et al. 2022

Cells

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“…Importantly, in most neurodegenerative disorders, the inflammation is not driven by a pathogen, suggesting that neuroinflammation might be triggered by autologous molecules. Excessive mitochondrial damage associated to impaired mitophagy, commonly observed in neurodegenerative disorders [ 91 ], can lead to the release of mtDAMPs into the cytoplasm and extracellular environment, thus enhancing the neuroinflammatory process [ 92 ]. Moreover, sustained mitochondrial dysfunction leads to cell death, which is aggravated in the CNS due to the high metabolic demand and the limited capacity of neuronal regeneration [ 84 ].…”

Section: Damage-associated Molecular Patterns Released From Mitochond...mentioning

confidence: 99%

Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders

Deus

Tavares

Beatriz

et al. 2022

Cells

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Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30–150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognised by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, mitochondrial transcription factor A (TFAM) and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EV release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

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“…Importantly, in most neurodegenerative disorders, the inflammation is not driven by a pathogen, suggesting that neuroinflammation might be triggered by autologous molecules. Excessive mitochondrial damage associated to impaired mitophagy, commonly observed in neurodegenerative disorders [87], can lead to the release of mtDAMPs into the cytoplasm and extracellular environment, thus enhancing the neuroinflammatory process [88]. Moreover, sustained mitochondrial dysfunction leads to cell death which is aggravated in the central nervous system (CNS) due to the high metabolic demand and the limited capacity of neuronal regeneration [80].…”

Section: Damage-associated Molecular Patterns (Damps) Released From M...mentioning

confidence: 99%

Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders

Lopes¹,

Mota²,

Deus³

et al. 2022

Preprint

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Neuroinflammation is a common hallmark in different neurodegenerative conditions that share neuronal dysfunction and a progressive loss of a selectively vulnerable brain cell population. Alongside ageing and genetics, inflammation, oxidative stress, and mitochondrial dysfunction are considered key risk factors. Microglia are considered immune sentinels of the central nervous system capable of initiating an innate and adaptive immune response. Nevertheless, the pathological mechanisms underlying the initiation and spread of inflammation in the brain are still poorly described. Recently, a new mechanism of intercellular signalling mediated by small extracellular vesicles (EVs) has been identified. EVs are nanosized particles (30-150 nm) with a bilipid membrane that carries cell-specific bioactive cargos that participate in physiological or pathological processes. Damage-associated molecular patterns (DAMPs) are cellular components recognized by the immune receptors of microglia, inducing or aggravating neuroinflammation in neurodegenerative disorders. Diverse evidence links mitochondrial dysfunction and inflammation mediated by mitochondrial-DAMPs (mtDAMPs) such as mitochondrial DNA, TFAM and cardiolipin, among others. Mitochondrial-derived vesicles (MDVs) are a subtype of EVs produced after mild damage to mitochondria and, upon fusion with multivesicular bodies (MVBs), are released as EVs to the extracellular space. MDVs are particularly enriched in mtDAMPs which can induce an immune response and the release of pro-inflammatory cytokines. Importantly, growing evidence supports the association between mitochondrial dysfunction, EVs release and inflammation. Here, we describe the role of extracellular vesicles-associated mtDAMPS in physiological conditions and as neuroinflammation activators contributing to neurodegenerative disorders.

show abstract

Mitophagy and Neurodegeneration: Between the Knowns and the Unknowns

Cited by 23 publications

References 284 publications

Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Autophagy: A Key Regulator of Homeostasis and Disease: An Overview of Molecular Mechanisms and Modulators

Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders

Mitochondrial Damage-Associated Molecular Patterns Content in Extracellular Vesicles Promotes Early Inflammation in Neurodegenerative Disorders

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