Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

Ji, Weike; Chakrabarti, Rajarshi; Fan, Xintao; Schoenfeld, Lori W.; Strack, Stefan; Higgs, Henry N.

doi:10.1083/jcb.201610057

Cited by 127 publications

(111 citation statements)

References 67 publications

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“…The latter study estimated that a functional DRP1 fission complex contains *100 DRP1 molecules. A population of DRP1 oligomers was detected on ER membranes, being distinct from mitochondrial or peroxisome-associated oligomers (162). On MFF knockdown, DRP1 oligomer levels at the ER, mitochondria, and peroxisomes were reduced, suggesting that DRP1 can use these three organelle membranes as oligomerization platforms.…”

Section: Fig 2 Selected Proteins Involved In Mitochondria-er Tethermentioning

confidence: 95%

Mitochondrial Morphofunction in Mammalian Cells

Bulthuis

Adjobo‐Hermans

Willems

et al. 2019

Antioxidants & Redox Signaling

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Significance: In addition to their classical role in cellular ATP production, mitochondria are of key relevance in various (patho)physiological mechanisms including second messenger signaling, neuro-transduction, immune responses and death induction. Recent Advances: Within cells, mitochondria are motile and display temporal changes in internal and external structure (''mitochondrial dynamics''). During the last decade, substantial empirical and in silico evidence was presented demonstrating that mitochondrial dynamics impacts on mitochondrial function and vice versa. Critical Issues: However, a comprehensive and quantitative understanding of the bidirectional links between mitochondrial external shape, internal structure and function (''morphofunction'') is still lacking. The latter particularly hampers our understanding of the functional properties and behavior of individual mitochondrial within single living cells. Future Directions: In this review we discuss the concept of mitochondrial morphofunction in mammalian cells, primarily using experimental evidence obtained within the last decade. The topic is introduced by briefly presenting the central role of mitochondria in cell physiology and the importance of the mitochondrial electron transport chain (ETC) therein. Next, we summarize in detail how mitochondrial (ultra)structure is controlled and discuss empirical evidence regarding the equivalence of mitochondrial (ultra)structure and function. Finally, we provide a brief summary of how mitochondrial morphofunction can be quantified at the level of single cells and mitochondria, how mitochondrial ultrastructure/volume impacts on mitochondrial bioreactions and intramitochondrial protein diffusion, and how mitochondrial morphofunction can be targeted by small molecules.

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Section: Fig 2 Selected Proteins Involved In Mitochondria-er Tethermentioning

confidence: 95%

Mitochondrial Morphofunction in Mammalian Cells

Bulthuis

Adjobo‐Hermans

Willems

et al. 2019

Antioxidants & Redox Signaling

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“…In addition to ER‐specific proteins regulating mitochondrial dynamics, a subpopulation of the tail‐anchored proteins MFF and FIS1 which are receptors for DRP1 recruitment on mitochondria also localize to the ER . MFF1 and FIS1 subsequently assemble DRP1 oligomers on ER, from where they can be transferred to the mitochondria or peroxisomes.…”

Section: Introductionmentioning

confidence: 99%

“…MFF1 and FIS1 subsequently assemble DRP1 oligomers on ER, from where they can be transferred to the mitochondria or peroxisomes. Additionally, fractions of ER‐localized MFF can also be transferred to the mitochondria or peroxisomes suggesting that ER can function as a platform for MFF‐mediated DRP1 oligomerization .…”

Section: Introductionmentioning

confidence: 99%

Causal roles of mitochondrial dynamics in longevity and healthy aging

et al. 2019

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Mitochondria are organized in the cell in the form of a dynamic, interconnected network. Mitochondrial dynamics, regulated by mitochondrial fission, fusion, and trafficking, ensure restructuring of this complex reticulum in response to nutrient availability, molecular signals, and cellular stress. Aberrant mitochondrial structures have long been observed in aging and age‐related diseases indicating that mitochondrial dynamics are compromised as cells age. However, the specific mechanisms by which aging affects mitochondrial dynamics and whether these changes are causally or casually associated with cellular and organismal aging is not clear. Here, we review recent studies that show specifically how mitochondrial fission, fusion, and trafficking are altered with age. We discuss factors that change with age to directly or indirectly influence mitochondrial dynamics while examining causal roles for altered mitochondrial dynamics in healthy aging and underlying functional outputs that might affect longevity. Lastly, we propose that altered mitochondrial dynamics might not just be a passive consequence of aging but might constitute an adaptive mechanism to mitigate age‐dependent cellular impairments and might be targeted to increase longevity and promote healthy aging.

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“…Given that mitochondria and ER have physical communication via the mitochondria‐fussed ER membrane, it is reasonable to assume that DRP1 plays an essential role in physiological and pathological processes, such as ER stress and energy metabolism on ER 11,12 . To support the hypothesis, oligomers of DRP1 has been reported to distribute on ER 13 . However, the signaling pathways that regulate ER translocalization of DRP1 and the potential function of ER‐located DRP1 remain to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

Yang

Mao

et al. 2020

FASEB j.

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Dynamin‐Related‐Protein 1 (DRP1) critically regulates mitochondrial and peroxisomal fission in multicellular organisms. However, the impact of DRP1 on other organelles, especially its direct influence on ER functions remains largely unclear. Here, we report that DRP1 translocates to endoplasmic reticulum (ER) in response to β‐adrenergic stimulation. To further investigate the function of DRP1 on ER‐lipid droplet (LD) dynamics and the metabolic subsequences, we generated an adipose tissue‐specific DRP1 knockout model (Adipo‐Drp1flx/flx). We found that the LDs in adipose tissues of Adipo‐Drp1flx/flx mice exhibited more unilocular morphology with larger sizes, and formed less multilocular structures upon cold exposure. Mechanistically, we discovered that abnormal LD morphology occurs because newly generated micro‐LDs fail to dissociate from the ER due to DRP1 ablation. Conversely, the ER retention of LDs can be rescued by the overexpressed DRP1 in the adipocytes. The alteration of LD dynamics, combined with abnormal mitochondrial and autophagy functions in adipose tissue, ultimately lead to abnormalities in lipid metabolism in Adipo‐Drp1flx/flx mice.

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Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

Abstract: Assembly of the dynamin GTPase Drp1 into constriction-competent oligomers is a key event in mitochondrial division. Here, Ji et al. show that Drp1 oligomerization can occur on endoplasmic reticulum through an ER-bound population of the tail-anchored protein Mff.

Cited by 127 publications

References 67 publications

Mitochondrial Morphofunction in Mammalian Cells

Mitochondrial Morphofunction in Mammalian Cells

Causal roles of mitochondrial dynamics in longevity and healthy aging

Novel role of dynamin‐related‐protein 1 in dynamics of ER‐lipid droplets in adipose tissue

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