INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division

Chakrabarti, Rajarshi; Ji, Weike; Stan, Radu V.; Juan-Sanz, Jaime de; Ryan, Timothy A.; Higgs, Henry N.

doi:10.1083/jcb.201709111

Cited by 270 publications

(342 citation statements)

References 71 publications

(143 reference statements)

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“…This constriction is mediated by actin filaments that accumulate between mitochondria and the ER and that are polymerized at the ER membrane by INF2 . INF2‐mediated actin polymerization leads to an accumulation of myosin type II , an increase in mitochondria–ER contacts, and the subsequent stimulation of mitochondrial Ca 2+ uptake before constriction of the IMM and mitochondrial division . The main driver of mitochondrial fission is the dynamin‐related GTPase DRP1, which moves from the cytosol to the OMM, where it interacts with membrane proteins such as FIS1, MFF, MiD49, and MiD51 .…”

Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 99%

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Metabolic implications of organelle–mitochondria communication

2019

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Cellular organelles are not static but show dynamism—a property that is likely relevant for their function. In addition, they interact with other organelles in a highly dynamic manner. In this review, we analyze the proteins involved in the interaction between mitochondria and other cellular organelles, especially the endoplasmic reticulum, lipid droplets, and lysosomes. Recent results indicate that, on one hand, metabolic alterations perturb the interaction between mitochondria and other organelles, and, on the other hand, that deficiency in proteins involved in the tethering between mitochondria and the ER or in specific functions of the interaction leads to metabolic alterations in a variety of tissues. The interaction between organelles is an emerging field that will permit to identify key proteins, to delineate novel modulation pathways, and to elucidate their implications in human disease.

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Section: Contacts Between Mitochondria and Other Organellesmentioning

confidence: 99%

“…Mitochondria-ER contacts are also increased in BAT after Ca 2+ treatment [94]. Moreover, MCU ablation in U2OS cells prevents mitochondrial division [61]. In addition to its role in mitochondrial dynamics, FUNDC1 interacts with the ER Ca 2+ channel IP3R2 and promotes Ca 2+ flux to mitochondria [76].…”

Section: Mitochondrial Dynamicsmentioning

confidence: 99%

Metabolic implications of organelle–mitochondria communication

2019

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“…ER tubules associate with and define mitochondrial fission sites [133]. While initial studies found that ER tubules wrap around mitochondria to mark the sites for DRP1 recruitment and constriction, new studies have revealed that the ER tubules can mediate DRP1-independent constriction of mitochondria [134]. Actin polymerization through ER-bound inverted formin 2 (INF2) results in force generation via myosin and initial constriction of mitochondria, which further enhances DRP1 oligomerization and DRP1-dependent constriction [134].…”

Section: Mitochondria-er Interactionsmentioning

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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“…In vitro GTPase assays show that Drp1 activity is greatly enhanced in the presence of actin filaments [48]. More recent work has shown that INF2 driven actin assembly at mitochondria-ER contacts also triggers calcium uptake into the mitochondria matrix which then synchronizes outer and inner membrane fission [49]. Taken together, these observations suggest that filamentous actin acts as an important regulator of inner and outer mitochondrial membrane fission.…”

Section: Actin Dynamics In Mitochondrial Motility and Remodelingmentioning

confidence: 99%

Mitochondrial-cytoskeletal interactions: dynamic associations that facilitate network function and remodeling

Moore

Holzbaur

2018

Current Opinion in Physiology

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Mitochondria are dynamic organelles that can form complex networks in the cell. These networks can be rapidly remodeled in response to environmental changes or to support cellular needs. Mitochondrial dynamics are dependent on interactions with the cellular cytoskeleton – both microtubules and actin filaments. Mitochondrial-cytoskeletal interactions have a well-established role in mitochondrial motility. Recent progress indicates that these interactions also regulate the balance of mitochondrial fission/fusion, as well as mitochondria turnover and mitochondrial inheritance during cell division. We review these advances, and how this work has deepened our understanding of mitochondrial dynamics in the cell.

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INF2-mediated actin polymerization at the ER stimulates mitochondrial calcium uptake, inner membrane constriction, and division

Cited by 270 publications

References 71 publications

Metabolic implications of organelle–mitochondria communication

Metabolic implications of organelle–mitochondria communication

Causal roles of mitochondrial dynamics in longevity and healthy aging

Mitochondrial-cytoskeletal interactions: dynamic associations that facilitate network function and remodeling

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