scholarly journals Mdm12p, a Component Required for Mitochondrial Inheritance That Is Conserved between Budding and Fission Yeast

1997 ◽  
Vol 136 (3) ◽  
pp. 545-553 ◽  
Author(s):  
Karen H. Berger ◽  
L. Farah Sogo ◽  
Michael P. Yaffe
Keyword(s):  
Membrane Protein ◽  
Fission Yeast ◽  
Outer Membrane ◽  
Subcellular Fractionation ◽  
Biochemical Properties ◽  
Dominant Negative ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Temperature Sensitive ◽  
Giant Mitochondria

Saccharomyces cerevisiae cells lacking the MDM12 gene product display temperature-sensitive growth and possess abnormally large, round mitochondria that are defective for inheritance by daughter buds. Analysis of the wild-type MDM12 gene revealed its product to be a 31-kD polypeptide that is homologous to a protein of the fission yeast Schizosaccharomyces pombe. When expressed in S. cerevisiae, the S. pombe Mdm12p homolog conferred a dominant-negative phenotype of giant mitochondria and aberrant mitochondrial distribution, suggesting partial functional conservation of Mdm12p activity between budding and fission yeast. The S. cerevisiae Mdm12p was localized by indirect immunofluorescence microscopy and by subcellular fractionation and immunodetection to the mitochondrial outer membrane and displayed biochemical properties of an integral membrane protein. Mdm12p is the third mitochondrial outer membrane protein required for normal mitochondrial morphology and distribution to be identified in S. cerevisiae and the first such mitochondrial component that is conserved between two different species.

scholarly journals Role of MMM1 in Maintaining Mitochondrial Morphology inNeurospora crassa

2000 ◽  
Vol 11 (9) ◽  
pp. 2961-2971 ◽  
Author(s):  
Holger Prokisch ◽  
Walter Neupert ◽  
Benedikt Westermann
Keyword(s):  
Outer Membrane ◽  
Transmembrane Domain ◽  
Female Sterility ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Temperature Sensitive ◽  
Dependent Manner ◽  
Giant Mitochondria ◽  
Mitochondrial Transport ◽  
General Importance

Mmm1p is a protein required for maintenance of mitochondrial morphology in budding yeast. It was proposed that it is required to mediate the interaction of the mitochondrial outer membrane with the actin cytoskeleton. We report the cloning and characterization of MMM1 of the filamentous fungus Neurospora crassa, an organism that uses microtubules for mitochondrial transport. Mutation of themmm-1 gene leads to a temperature-sensitive slow growth phenotype and female sterility. Mutant cells harbor abnormal giant mitochondria at all stages of the asexual life cycle, whereas actin filament-depolymerizing drugs have no effect on mitochondrial morphology. The MMM1 protein has a single transmembrane domain near the N terminus and exposes a large C-terminal domain to the cytosol. The protein can be imported into the outer membrane in a receptor-dependent manner. Our findings suggest that MMM1 is a factor of general importance for mitochondrial morphology independent of the cytoskeletal system used for mitochondrial transport.

scholarly journals The Dynamin-Related Gtpase, Mgm1p, Is an Intermembrane Space Protein Required for Maintenance of Fusion Competent Mitochondria

2000 ◽  
Vol 151 (2) ◽  
pp. 341-352 ◽  
Author(s):  
Edith D. Wong ◽  
Jennifer A. Wagner ◽  
Steven W. Gorsich ◽  
J. Michael McCaffery ◽  
Janet M. Shaw ◽  
...  
Keyword(s):  
Outer Membrane ◽  
Mitochondrial Fission ◽  
Mitochondrial Fusion ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Temperature Sensitive ◽  
Intermembrane Space ◽  
Direct Role ◽  
Membrane Fission ◽  
Mitochondrial Intermembrane Space

Mutations in the dynamin-related GTPase, Mgm1p, have been shown to cause mitochondrial aggregation and mitochondrial DNA loss in Saccharomyces cerevisiae cells, but Mgm1p's exact role in mitochondrial maintenance is unclear. To study the primary function of MGM1, we characterized new temperature sensitive MGM1 alleles. Examination of mitochondrial morphology in mgm1 cells indicates that fragmentation of mitochondrial reticuli is the primary phenotype associated with loss of MGM1 function, with secondary aggregation of mitochondrial fragments. This mgm1 phenotype is identical to that observed in cells with a conditional mutation in FZO1, which encodes a transmembrane GTPase required for mitochondrial fusion, raising the possibility that Mgm1p is also required for fusion. Consistent with this idea, mitochondrial fusion is blocked in mgm1 cells during mating, and deletion of DNM1, which encodes a dynamin-related GTPase required for mitochondrial fission, blocks mitochondrial fragmentation in mgm1 cells. However, in contrast to fzo1 cells, deletion of DNM1 in mgm1 cells restores mitochondrial fusion during mating. This last observation indicates that despite the phenotypic similarities observed between mgm1 and fzo1 cells, MGM1 does not play a direct role in mitochondrial fusion. Although Mgm1p was recently reported to localize to the mitochondrial outer membrane, our studies indicate that Mgm1p is localized to the mitochondrial intermembrane space. Based on our localization data and Mgm1p's structural homology to dynamin, we postulate that it functions in inner membrane remodeling events. In this context, the observed mgm1 phenotypes suggest that inner and outer membrane fission is coupled and that loss of MGM1 function may stimulate Dnm1p-dependent outer membrane fission, resulting in the formation of mitochondrial fragments that are structurally incompetent for fusion.

scholarly journals Sam50-Mic19-Mic60 axis Determines Mitochondrial Cristae Architecture by Mediating Mitochondrial Outer and Inner Membrane Contact

2018 ◽  
Author(s):  
Junhui Tang ◽  
Kuan Zhang ◽  
Jun Dong ◽  
Chaojun Yan ◽  
Shi Chen ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Outer Membrane ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Intermembrane Space ◽  
Inner Membrane ◽  
Atp Production ◽  
Mitochondrial Intermembrane Space ◽  
Membrane Contact ◽  
Inner Membrane Protein

ABSTRACTMitochondrial cristae are critical for efficient oxidative phosphorylation, however, how cristae architecture is precisely organized remains largely unknown. Here, we discovered that Mic19, a core component of MICOS (mitochondrial contact site and cristae organizing system) complex, can be cleaved at N-terminal by mitochondrial protease OMA1. Mic19 directly interacts with mitochondrial outer-membrane protein Sam50 (the key subunit of SAM complex) and inner-membrane protein Mic60 (the key component of MICOS complex) to form Sam50-Mic19-Mic60 axis, which dominantly connects SAM and MICOS complexes to assemble MIB (mitochondrial intermembrane space bridging) supercomplex for mediating mitochondrial outer- and inner-membrane contact. OMA1-mediated Mic19 cleavage causes Sam50-Mic19-Mic60 axis disruption, which separates SAM and MICOS and leads to MIB disassembly. Disrupted Sam50-Mic19-Mic60 axis, even in the presence of SAM and MICOS complexes, causes the abnormal mitochondrial morphology, loss of mitochondrial cristae junctions, abnormal cristae distribution and reduced ATP production. Importantly, Sam50 displays punctate distribution at mitochondrial outer membrane, and acts as an anchoring point to guide the formation of mitochondrial cristae junctions. Therefore, we propose a model that Sam50-Mic19-Mic60 axis mediated SAM-MICOS complexes integration determines mitochondrial cristae architecture.

scholarly journals Regulation of mitochondrial morphology and inheritance by Mdm10p, a protein of the mitochondrial outer membrane.

1994 ◽  
Vol 126 (6) ◽  
pp. 1361-1373 ◽  
Author(s):  
L F Sogo ◽  
M P Yaffe
Keyword(s):  
Outer Membrane ◽  
Yeast Cells ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Wild Type ◽  
Giant Mitochondria ◽  
Mitochondrial Distribution ◽  
Rapid Restoration ◽  
Mutant Phenotypes ◽  
Mutant Cells

Yeast cells with the mdm10 mutation possess giant spherical mitochondria and are defective for mitochondrial inheritance. The giant mitochondria display classical features of mitochondrial ultrastructure, yet they appear incapable of movement or division. Genetic analysis indicated that the mutant phenotypes resulted from a single nuclear mutation, and the isolated MDM10 gene restored wild-type mitochondrial distribution and morphology when introduced into mutant cells. MDM10 encodes a protein of 56.2 kD located in the mitochondrial outer membrane. Depletion of Mdm10p from cells led to a condensation of normally extended, tubular mitochondria into giant spheres, and reexpression of the protein resulted in a rapid restoration of normal mitochondrial morphology. These results demonstrate that Mdm10p can control mitochondrial morphology, and that it plays a role in the inheritance of mitochondria.

scholarly journals MMM1 encodes a mitochondrial outer membrane protein essential for establishing and maintaining the structure of yeast mitochondria.

1994 ◽  
Vol 126 (6) ◽  
pp. 1375-1391 ◽  
Author(s):  
S M Burgess ◽  
M Delannoy ◽  
R E Jensen
Keyword(s):  
Outer Membrane ◽  
Cell Function ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Temperature Sensitive ◽  
Restrictive Temperature ◽  
Cell Periphery ◽  
Permissive Temperature ◽  
Yeast Saccharomyces Cerevisiae ◽  
Mitochondrial Structure

In the yeast Saccharomyces cerevisiae, mitochondria are elongated organelles which form a reticulum around the cell periphery. To determine the mechanism by which mitochondrial shape is established and maintained, we screened yeast mutants for those defective in mitochondrial morphology. One of these mutants, mmm1, is temperature-sensitive for the external shape of its mitochondria. At the restrictive temperature, elongated mitochondria appear to quickly collapse into large, spherical organelles. Upon return to the permissive temperature, wild-type mitochondrial structure is restored. The morphology of other cellular organelles is not affected in mmm1 mutants, and mmm1 does not disrupt normal actin or tubulin organization. Cells disrupted in the MMM1 gene are inviable when grown on nonfermentable carbon sources and show abnormal mitochondrial morphology at all temperatures. The lethality of mmm1 mutants appears to result from the inability to segregate the aberrant-shaped mitochondria into daughter cells. Mitochondrial structure is therefore important for normal cell function. Mmm1p is located in the mitochondrial outer membrane, with a large carboxyl-terminal domain facing the cytosol. We propose that Mmm1p maintains mitochondria in an elongated shape by attaching the mitochondrion to an external framework, such as the cytoskeleton.

scholarly journals A novel mitochondrial outer membrane protein, MOMA-1, that affects cristae morphology in Caenorhabditis elegans

2011 ◽  
Vol 22 (6) ◽  
pp. 831-841 ◽  
Author(s):  
Brian P. Head ◽  
Miren Zulaika ◽  
Sergey Ryazantsev ◽  
Alexander M. van der Bliek
Keyword(s):  
Caenorhabditis Elegans ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Morphology ◽  
Intermembrane Space ◽  
The Novel ◽  
Metabolic Functions ◽  
Mitochondrial Staining

 Three proteins with similar effects on mitochondrial morphology were identified in an RNA interference (RNAi) screen for mitochondrial abnormalities in Caenorhabditis elegans. One of these is the novel mitochondrial outer membrane protein MOMA-1. The second is the CHCHD3 homologue, CHCH-3, a small intermembrane space protein that may act as a chaperone. The third is a mitofilin homologue, IMMT-1. Mitofilins are inner membrane proteins that control the shapes of cristae. RNAi or mutations in each of these genes change the relatively constant diameters of mitochondria into highly variable diameters, ranging from thin tubes to localized swellings. Neither growth nor brood size of the moma-1, chch-3, or immt-1 single mutants is affected, suggesting that their metabolic functions are normal. However, growth of moma-1 or immt-1 mutants on chch-3(RNAi) leads to withered gonads, a lack of mitochondrial staining, and a dramatic reduction in fecundity, while moma-1; immt-1 double mutants are indistinguishable from single mutants. Mutations in moma-1 and immt-1 also have similar effects on cristae morphology. We conclude that MOMA-1 and IMMT-1 act in the same pathway. It is likely that the observed effects on mitochondrial diameter are an indirect effect of disrupting cristae morphology.

scholarly journals Mutations in Fis1 disrupt orderly disposal of defective mitochondria

2014 ◽  
Vol 25 (1) ◽  
pp. 145-159 ◽  
Author(s):  
Qinfang Shen ◽  
Koji Yamano ◽  
Brian P. Head ◽  
Sumihiro Kawajiri ◽  
Jesmine T. M. Cheung ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Membrane Protein ◽  
Outer Membrane ◽  
Outer Membrane Protein ◽  
Couple Stress ◽  
Mitochondrial Fission ◽  
Mitochondrial Outer Membrane ◽  
Related Protein ◽  
Degradation Processes ◽  
Mitochondrial Toxins

Mitochondrial fission is mediated by the dynamin-related protein Drp1 in metazoans. Drp1 is recruited from the cytosol to mitochondria by the mitochondrial outer membrane protein Mff. A second mitochondrial outer membrane protein, named Fis1, was previously proposed as recruitment factor, but Fis1−/− cells have mild or no mitochondrial fission defects. Here we show that Fis1 is nevertheless part of the mitochondrial fission complex in metazoan cells. During the fission cycle, Drp1 first binds to Mff on the surface of mitochondria, followed by entry into a complex that includes Fis1 and endoplasmic reticulum (ER) proteins at the ER–mitochondrial interface. Mutations in Fis1 do not normally affect fission, but they can disrupt downstream degradation events when specific mitochondrial toxins are used to induce fission. The disruptions caused by mutations in Fis1 lead to an accumulation of large LC3 aggregates. We conclude that Fis1 can act in sequence with Mff at the ER–mitochondrial interface to couple stress-induced mitochondrial fission with downstream degradation processes.

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