Mitochondrial dynamics in adaptive and maladaptive cellular stress responses

Eisner, Verónica; Picard, Martin; Hajnóczky, György

doi:10.1038/s41556-018-0133-0

Cited by 429 publications

(354 citation statements)

References 180 publications

(237 reference statements)

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“…Previously (still currently in undergraduate textbooks) depicted to be discrete bean-shaped organelles free in the cytoplasm of cells, mitochondria are now known to be more complex and dynamic in their morphology, arrangement and subcellular distribution (Tilokani et al, 2018, Wai andLanger, 2016). Mitochondria undergo continuous cycles of fusion and fission and are redistributed within the cell to areas requiring energy production (Eisner et al, 2018). Mitochondrial movement, fusion and fission are dependent on the cell cytoskeleton, both actin and microtubular, and mediated by actin and microtubule motor proteins (Woods et al, 2016).…”

Section: Mitochondrial Morphology and Traffickingmentioning

confidence: 99%

The Dictyostelium model for mitochondrial biology and disease

Pearce¹,

Annesley²,

Fisher³

2019

Int. J. Dev. Biol.

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The unicellular slime mould Dictyostelium discoideum is a valuable eukaryotic model organism in the study of mitochondrial biology and disease. As a member of the Amoebozoa, a sister clade to the animals and fungi, Dictyostelium mitochondrial biology shares commonalities with these organisms, but also exhibits some features of plants. As such it has made significant contributions to the study of eukaryotic mitochondrial biology. This review provides an overview of the advances in mitochondrial biology made by the study of Dictyostelium and examines several examples where Dictyostelium has and will contribute to the understanding of mitochondrial disease. The study of Dictyostelium's mitochondrial biology has contributed to the understanding of mitochondrial genetics, transcription, protein import, respiration, morphology and trafficking, and the role of mitochondria in cellular differentiation. Dictyostelium is also proving to be a versatile model organism in the study both of classical mitochondrial disease e.g. Leigh syndrome, and in mitochondria-associated neurodegenerative diseases like Parkinson's disease. The study of mitochondrial diseases presents a unique challenge due to the cryptic nature of their genotypephenotype relationship. The use of Dictyostelium can contribute to resolving this problem by providing a genetically tractable, haploid eukaryotic organism with a suite of readily characterised phenotype readouts of cellular signalling pathways. Dictyostelium has provided insight into the signalling pathways involved in multiple neurodegenerative diseases and will continue to provide a significant contribution to the understanding of mitochondrial biology and disease.

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Section: Mitochondrial Morphology and Traffickingmentioning

confidence: 99%

The Dictyostelium model for mitochondrial biology and disease

Pearce¹,

Annesley²,

Fisher³

2019

Int. J. Dev. Biol.

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“…Mitochondrial function is intimately linked to its dynamically regulated architecture; mitochondria undergo fusion and fission, and the balance of these two processes determines the mitochondrial architecture. Various cellular stressors alter mitochondrial function, and changes in mitochondrial structure enable the cell to restore the mitochondrial homeostasis (5).…”

Section: Ethanol Causes Mitochondrial Fragmentation In C Elegans Musmentioning

confidence: 99%

“…Mitochondria are not only responsible for cellular energy production but also central to cellular signaling, metabolism, and cell death. These functions are closely linked to their architecture, which is dynamically regulated by fission and fusion processes in response to stress and metabolic state (5). Mitochondrial fission is mediated by the dynaminrelated protein DRP1.…”

Section: Introductionmentioning

confidence: 99%

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

Hong-kyun

2019

Preprint

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AbstractsChronic excessive ethanol consumption produces distinct toxic and adverse effects on different tissues. In skeletal muscle ethanol causes alcoholic myopathy characterized by myofiber atrophy and loss of muscle strength. Alcoholic myopathy is more prevalent than all inherited muscle diseases combined. Current evidence indicates that ethanol directly impairs muscle organization and function. However, the underlying mechanism by which ethanol causes its toxicity to muscle is poorly understood. Here, we show that the nematode C. elegans recapitulates key aspects of alcoholic myopathy when exposed to ethanol. As in mammals, ethanol exposure impairs muscle strength and organization and induces the expression of protective genes, including oxidative stress response. In addition, ethanol exposure causes a fragmentation of mitochondrial networks aligned with myofibril lattices. This ethanol-induced mitochondrial fragmentation is dependent on mitochondrial fission factor DRP-1 (dynamin-like protein 1), and its receptor proteins on the mitochondrial outer membrane. Our data indicate that this fragmentation contributes to activation of mitochondrial unfolded protein response (UPR). We also found that robust perpetual mitochondrial UPR activation effectively counters muscle weakness caused by ethanol exposure. Our results strongly suggest that modulation of mitochondrial stress responses provides a mechanism to ameliorate alcohol toxicity and damage to muscle.SignificanceChronic alcohol abuse causes the damage and toxicity to peripheral tissues, including muscle. Alcohol perturbs the structure and function of striated skeletal and cardiac muscles. These toxic effects of alcohol on striated muscles negatively impact morbidity and mortality to alcohol misusers. Here, we demonstrate that the nematode C. elegans also exhibits key features of alcoholic myopathy when exposed to ethanol. Ethanol exposure impairs muscle organization and strength, and induces the expression of genes that cope with alcohol toxicity. Particularly, we find that ethanol toxicity is centered on mitochondria, the power plants of the cell. As an adaptive protective response to mitochondrial dysfunction, ethanol-exposed cells induce global transcriptional reprogramming to restore normal mitochondrial function. Upregulation of this transcriptional reprogramming in C. elegans effectively blocks ethanol-induced muscle weakness, a key feature of alcoholic myopathy. Thus, the modulation of mitochondrial stress responses is a potentially promising therapeutic strategy to ameliorate alcohol toxicity to muscle.

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“…Fission is followed by fusion, which is coordinated by the inner and outer mitochondrial proteins such as mitofusin (MFN)-1 and -2 and optic atrophy 1 (OPA1) (Westermann, 2002;Zhang & Chan, 2007). Studies have shown that the dysregulation of mitochondrial dynamics has a profound effect on cellular energetics which in turn could affect their function (Eisner, Picard, & Hajnoczky, 2018;Mishra & Chan, 2016). For instance, impairment in mitochondrial fragmentation decreases the reprogramming and differentiation efficiency of the progenitor cells (Forni, Peloggia, Trudeau, Shirihai, & Kowaltowski, 2016).…”

Section: Introductionmentioning

confidence: 99%

An indispensable role for dynamin-related protein 1 (DRP1) in adipogenesis

Mukhi

Chen

et al. 2020

Preprint

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Emerging evidence indicates that proper mitochondrial dynamics is critical for adipocyte differentiation and functional thermogenic capacity. We found that mitochondrial fission protein dynamin-related protein 1 (DRP1) is highly expressed in brown adipose tissue compared to white adipose tissue and their levels increase during brown adipocyte differentiation. Our results reveal that the inhibition of DRP1 using Mdivi-1 mitigates adipocyte differentiation and differentiation-associated mitochondrial biogenesis. We found that DRP1 is essential for the induction of the early phase of adipogenic transcriptional program. Intriguingly, inhibition of DRP1 is dispensable following the induction of adipogenesis and adipogenesis-associated mitochondrial biogenesis. Together, we demonstrate that DRP1 in the preadipocytes plays an essential role in brown and beige adipogenesis.

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Mitochondrial dynamics in adaptive and maladaptive cellular stress responses

Cited by 429 publications

References 180 publications

The Dictyostelium model for mitochondrial biology and disease

The Dictyostelium model for mitochondrial biology and disease

Alcohol induces mitochondrial fragmentation and stress responses to maintain normal muscle function in Caenorhabditis elegans

An indispensable role for dynamin-related protein 1 (DRP1) in adipogenesis

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