Mdv1 Interacts with Assembled Dnm1 to Promote Mitochondrial Division

Naylor, Kari; Ingerman, Elena; Okreglak, Voytek; Marino, Matthew; Hinshaw, Jenny E.; Nunnari, Jodi

doi:10.1074/jbc.m507943200

Cited by 131 publications

(151 citation statements)

References 31 publications

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“…Mda1 appears as a medial belt in the early stage of mitochondrial division, before Dnm1 accumulation. In yeasts, exogenously expressed dsRed-Mdv1 follows GFP-Dnm1 accumulation (25), whereas genetic studies indicated that Mdv1 and Caf4 function upstream of Dnm1 (24). Our biochemical experiments as well as localization studies suggested that Mda1 exists as a stable homo-oligomer independently of Dnm1.…”

Section: Discussionmentioning

confidence: 78%

“…Fis1 mediates Dnm1 localization to mitochondrial surface through Mdv1 or Caf4 (21,23,24). The modes of their interaction are still open to discussion, and additional or distinctive roles for Mdv1 and Caf4 are also suggested (24)(25)(26)(27). Orthologs for Mdv1 or Caf4 have not been found in other organisms whereas potent Fis1 orthologs have been characterized in human (7,28) and plants (29).…”

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confidence: 99%

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WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae

Nishida

Yagisawa²,

Kuroiwa³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Mitochondria are not produced de novo but are maintained by division. Mitochondrial division is a coordinated process of positioning and constriction of the division site and fission of double membranes, in which dynamin-related protein is believed to mediate outer membrane fission. Part of the mitochondrial division machinery was purified from M phase-arrested Cyanidioschyzon merolae cells through biochemical fractionation. The dynaminrelated protein Dnm1 was one of the two major proteins in the purified fraction and was accompanied by a newly identified protein CMR185C, named Mda1. Mda1 contained a predictable coiled-coil region and WD40 repeats, similarly to Mdv1 and Caf4 in yeasts. Immunofluorescence and immunoelectron microscopy showed that Mda1 localizes as a medial belt or ring on the mitochondrial outer surface throughout the division. The ring formation of Mda1 followed the plane of the ring of FtsZ, a protein that resides in the matrix. Dnm1 consistently colocalized with Mda1 only in the late stages of division. Mda1 protein was expressed through S to M phases and was phosphorylated specifically in M phase when Mda1 transformed from belt into foci and became colocalizing with Dnm1. Dephosphorylation of Mda1 in vitro increased its sedimentation coefficient, suggesting conformational changes of the macromolecule. Disassembly of the purified mitochondrial division machinery was performed by adding GTP to independently release Dnm1, suggesting that Mda1 forms a stable homo-oligomer by itself as a core structure of the mitochondrial division machinery.

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae

Nishida

Yagisawa²,

Kuroiwa³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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“…Strains W303 ( ade2–1; leu2–3; his3–11, 15; trp1–1; ura3–1; can1–100 ) [31], W303 NUM1-yEGFP::HIS , W303 Δ num1::HIS , W303 Δ dyn1::HIS, and W303 fzo1-1 Δ dnm1::HIS Δ num1::KAN [10], W303 NUM1-yEGFP::KAN [12], W303 fzo1-1 [24], and W303 DYN1-mKate::HIS , Δ kar9::NATNT2 , and W303 MMR1-AID-FLAG::HYG Δ ypt11::NATNT2 TIR1::URA ( mito AID ) [17] were described previously.…”

Section: Methodsmentioning

confidence: 99%

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

et al. 2018

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Organelle distribution is regulated over the course of the cell cycle to ensure that each of the cells produced at the completion of division inherits a full complement of organelles. In yeast, the protein Num1 functions in the positioning and inheritance of two essential organelles, mitochondria and the nucleus. Specifically, Num1 anchors mitochondria as well as dynein to the cell cortex, and this anchoring activity is required for proper mitochondrial distribution and dynein-mediated nuclear inheritance. The assembly of Num1 into clusters at the plasma membrane is critical for both of its anchoring functions. We have previously shown that mitochondria drive the assembly of Num1 clusters and that these mitochondria-assembled Num1 clusters serve as cortical attachment sites for dynein. Here we further examine the role for mitochondria in dynein anchoring. Using a GFP-αGFP nanobody targeting system, we synthetically clustered Num1 on eisosomes to bypass the requirement for mitochondria in Num1 cluster formation. Utilizing this system, we found that mitochondria positively impact the ability of synthetically clustered Num1 to anchor dynein and support dynein function even when mitochondria are no longer required for cluster formation. Thus, the role of mitochondria in regulating dynein function extends beyond simply concentrating Num1; mitochondria likely promote an arrangement of Num1 within a cluster that is competent for dynein anchoring. This functional dependency between mitochondrial and nuclear positioning pathways likely serves as a mechanism to order and integrate major cellular organization systems over the course of the cell cycle.

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“…The small outer mitochondrial membrane protein Fis1 recruits cytosolic Dnm1/Drp1, facilitating its ability to cycle on and off mitochondria. The interaction of yeast Fis1 and Dnm1/Drp1 is mediated by bridging molecules (Tieu and Nunnari, 2000;Cerveny and Jensen, 2003;Griffin et al, 2005;Karren et al, 2005;Naylor et al, 2006). The bridging factor Mdv1/Net2 is a WD repeat protein that has a partially redundant function with its closest homologue Caf4 (Griffin et al, 2005).…”

Section: 'Day Jobs' For Pro-death Mitochondrial Proteinsmentioning

confidence: 99%

Mitochondrial factors with dual roles in death and survival

Berman

Ivanovska

et al. 2006

Oncogene

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At least in mammals, we have some understanding of how caspases facilitate mitochondria-mediated cell death, but the biochemical mechanisms by which other factors promote or inhibit programmed cell death are not understood. Moreover, most of these factors are only studied after treating cells with a death stimulus. A growing body of new evidence suggests that cell death regulators also have 'day jobs' in healthy cells. Even caspases, mitochondrial fission proteins and pro-death Bcl-2 family proteins appear to have normal cellular functions that promote cell survival. Here, we review some of the supporting evidence and stretch beyond the evidence to seek an understanding of the remaining questions.

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Mdv1 Interacts with Assembled Dnm1 to Promote Mitochondrial Division

Cited by 131 publications

References 31 publications

WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae

WD40 protein Mda1 is purified with Dnm1 and forms a dividing ring for mitochondria before Dnm1 in Cyanidioschyzon merolae

The role of mitochondria in anchoring dynein to the cell cortex extends beyond clustering the anchor protein

Mitochondrial factors with dual roles in death and survival

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