Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria

Kruppa, Antonina J.; Kishi‐Itakura, Chieko; Masters, Thomas A.; Rorbach, Joanna; Grice, Guinevere L.; Kendrick‐Jones, John; Nathan, James A.; Minczuk, Michal; Buß, Folma

doi:10.1016/j.devcel.2018.01.007

Cited by 86 publications

(83 citation statements)

References 58 publications

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“…MYO6 was shown promote F‐actin encapsulating waves to sequester mitochondria destined for degradation. Consistent with this role, MYO6 was required for full mitochondrial operating capacity . From these studies, we see a divergent role for MYO6 in the mitophagy cascade.…”

Section: Actin‐based Mitochondrial Movementsupporting

confidence: 56%

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Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

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Caino

2019

Cancer Reports

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Background Mammalian cells must constantly reprogram the distribution of mitochondria in order to meet the local demands for energy, calcium, redox balance, and other mitochondrial functions. Mitochondrial localization inside the cell is a result of a combination of movement along the microtubule tracks plus anchoring to actin filaments. Recent findings Recent advances show that subcellular distribution of mitochondria can regulate tumor cell growth, proliferation/motility plasticity, metastatic competence, and therapy responses in tumors. In this review, we discuss our current understanding of the mechanisms by which mitochondrial subcellular distribution is regulated in tumor cells. Conclusions Mitochondrial trafficking is dysregulated in tumors. Accumulation of mitochondria at the leading edge of the cell supports energy expensive processes of focal adhesion dynamics, cell membrane dynamics, migration, and invasion.

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Section: Actin‐based Mitochondrial Movementsupporting

confidence: 56%

“…was required for full mitochondrial operating capacity. 71,72 From these studies, we see a divergent role for MYO6 in the mitophagy cascade.…”

Section: Figurementioning

confidence: 85%

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

Furnish

Caino

2019

Cancer Reports

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“…Furthermore, during mitophagy, the pathway for removal of nonfunctional mitochondria via autophagy, MYO6 is selectively recruited to damaged mitochondria. MYO6 recruitment does not depend on optineurin, TAX1BP1 and NDP52 but requires its ubiquitin‐binding domain . MYO6 induces the formation of actin cages around damaged mitochondria thereby isolating dysfunctional mitochondria destined for mitophagy from the healthy network.…”

Section: Cellular Functions Of Myo6mentioning

confidence: 99%

“…Through the ABD1/MyUb domain MYO6 can either interact directly with adaptor proteins such as GIPC, TAX1BP1, NDP52 and optineurin or indirectly via ubiquitin chains to other proteins. MYO6 has been shown, for example, to bind to ubiquitinated proteins on the outer mitochondrial membrane . In addition, indirect binding via free ubiquitin chains between MYO6 and adaptor proteins that contain a ubiquitin‐binding domain, such as TAX1BP1 and optineurin has been suggested .…”

Section: Myo6 Molecular Interactionsmentioning

confidence: 99%

“…Interestingly, this region is dispensable for ubiquitin binding, but essential for direct adaptor binding. In contrast to GIPC, NDP52, TAX1BP1 and optineurin not only interact directly with MYO6 [51,52], but potentially also bind indirectly via ubiquitin chains to the MYO6 MyUb domain [21,22]. MYO6 interacts with K48, K63, K29 and K11 linked ubiquitin chains, with a clear preference for the latter three [21].…”

Section: Myo6 Abd1 and Myub Domain Encompassing The Rrl Motifmentioning

confidence: 99%

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TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

et al. 2019

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Myosins of class VI (MYO6) are unique actin‐based motor proteins that move cargo towards the minus ends of actin filaments. As the sole myosin with this directionality, it is critically important in a number of biological processes. Indeed, loss or overexpression of MYO6 in humans is linked to a variety of pathologies including deafness, cardiomyopathy, neurodegenerative diseases as well as cancer. This myosin interacts with a wide variety of direct binding partners such as for example the selective autophagy receptors optineurin, TAX1BP1 and NDP52 and also Dab2, GIPC, TOM1 and LMTK2, which mediate distinct functions of different MYO6 isoforms along the endocytic pathway. Functional proteomics has recently been used to identify the wider MYO6 interactome including several large functionally distinct multi‐protein complexes, which highlight the importance of this myosin in regulating the actin and septin cytoskeleton. Interestingly, adaptor‐binding not only triggers cargo attachment, but also controls the inactive folded conformation and dimerisation of MYO6. Thus, the C‐terminal tail domain mediates cargo recognition and binding, but is also crucial for modulating motor activity and regulating cytoskeletal track dynamics.

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The MyMOMA domain of MYO19 encodes for distinct Miro‐dependent and Miro‐independent mechanisms of interaction with mitochondrial membranes

et al. 2019

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MYO19 interacts with mitochondria through a C‐terminal membrane association domain (MyMOMA). Specific mechanisms for localization of MYO19 to mitochondria are poorly understood. Using promiscuous biotinylation data in combination with existing affinity‐capture databases, we have identified a number of putative MYO19‐interacting proteins. We chose to explore the interaction between MYO19 and the mitochondrial GTPase Miro2 by expressing mchr‐Miro2 in combination with GFP‐tagged fragments of the MyMOMA domain and assaying for recruitment of MYO19‐GFP to mitochondria. Coexpression of MYO19898‐970‐GFP with mchr‐Miro2 enhanced MYO19898‐970‐GFP localization to mitochondria. Mislocalizing Miro2 to filopodial tips or the cytosolic face of the nuclear envelope did not recruit MYO19898‐970‐GFP to either location. To address the kinetics of the Miro2/MYO19 interaction, we used FRAP analysis and permeabilization‐activated reduction in fluorescence analysis. MyMOMA constructs containing a putative membrane‐insertion motif but lacking the Miro2‐interacting region displayed slow exchange kinetics. MYO19898‐970‐GFP, which does not include the membrane‐insertion motif, displayed rapid exchange kinetics, suggesting that MYO19 interacting with Miro2 has higher mobility than MYO19 inserted into the mitochondrial outer membrane. Mutation of well‐conserved, charged residues within MYO19 or within the switch I and II regions of Miro2 abolished the enhancement of MYO19898‐970‐GFP localization in cells ectopically expressing mchr‐Miro2. Additionally, expressing mutant versions of Miro2 thought to represent particular nucleotide states indicated that the enhancement of MYO19898‐970‐GFP localization is dependent on Miro2 nucleotide state. Taken together, these data suggest that membrane‐inserted MYO19 is part of a larger complex, and that Miro2 plays a role in integration of actin‐ and microtubule‐based mitochondrial activities.

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Myosin VI-Dependent Actin Cages Encapsulate Parkin-Positive Damaged Mitochondria

Cited by 86 publications

References 58 publications

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

Altered mitochondrial trafficking as a novel mechanism of cancer metastasis

TheMYO6 interactome: selective motor‐cargo complexes for diverse cellular processes

The MyMOMA domain of MYO19 encodes for distinct Miro‐dependent and Miro‐independent mechanisms of interaction with mitochondrial membranes

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