scholarly journals Fis1, Mff, MiD49, and MiD51 mediate Drp1 recruitment in mitochondrial fission

2013 ◽  
Vol 24 (5) ◽  
pp. 659-667 ◽  
Author(s):  
Oliver C. Losón ◽  
Zhiyin Song ◽  
Hsiuchen Chen ◽  
David C. Chan
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Mitochondrial Dynamics ◽  
Mitochondrial Fission ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane ◽  
Related Protein ◽  
Immunofluorescence Analysis ◽  
Multiple Receptors ◽  
Mitochondrial Elongation

Several mitochondrial outer membrane proteins—mitochondrial fission protein 1 (Fis1), mitochondrial fission factor (Mff), mitochondrial dynamics proteins of 49 and 51 kDa (MiD49 and MiD51, respectively)—have been proposed to promote mitochondrial fission by recruiting the GTPase dynamin-related protein 1 (Drp1), but fundamental issues remain concerning their function. A recent study supported such a role for Mff but not for Fis1. In addition, it is unclear whether MiD49 and MiD51 activate or inhibit fission, because their overexpression causes extensive mitochondrial elongation. It is also unknown whether these proteins can act in the absence of one another to mediate fission. Using Fis1-null, Mff-null, and Fis1/Mff-null cells, we show that both Fis1 and Mff have roles in mitochondrial fission. Moreover, immunofluorescence analysis of Drp1 suggests that Fis1 and Mff are important for the number and size of Drp1 puncta on mitochondria. Finally, we find that either MiD49 or MiD51 can mediate Drp1 recruitment and mitochondrial fission in the absence of Fis1 and Mff. These results demonstrate that multiple receptors can recruit Drp1 to mediate mitochondrial fission.

scholarly journals Role of Phosphatidylethanolamine in the Biogenesis of Mitochondrial Outer Membrane Proteins

2013 ◽  
Vol 288 (23) ◽  
pp. 16451-16459 ◽  
Author(s):  
Thomas Becker ◽  
Susanne E. Horvath ◽  
Lena Böttinger ◽  
Natalia Gebert ◽  
Günther Daum ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Proper Function ◽  
Mitochondrial Outer Membrane ◽  
Tom Complex ◽  
Precursor Proteins ◽  
Helical Proteins ◽  
The Stability

The mitochondrial outer membrane contains proteinaceous machineries for the import and assembly of proteins, including TOM (translocase of the outer membrane) and SAM (sorting and assembly machinery). It has been shown that the dimeric phospholipid cardiolipin is required for the stability of TOM and SAM complexes and thus for the efficient import and assembly of β-barrel proteins and some α-helical proteins of the outer membrane. Here, we report that mitochondria deficient in phosphatidylethanolamine (PE), the second non-bilayer-forming phospholipid, are impaired in the biogenesis of β-barrel proteins, but not of α-helical outer membrane proteins. The stability of TOM and SAM complexes is not disturbed by the lack of PE. By dissecting the import steps of β-barrel proteins, we show that an early import stage involving translocation through the TOM complex is affected. In PE-depleted mitochondria, the TOM complex binds precursor proteins with reduced efficiency. We conclude that PE is required for the proper function of the TOM complex.

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.

scholarly journals Interaction between Mitochondria and the Actin Cytoskeleton in Budding Yeast Requires Two Integral Mitochondrial Outer Membrane Proteins, Mmm1p and Mdm10p

1998 ◽  
Vol 141 (6) ◽  
pp. 1371-1381 ◽  
Author(s):  
Istvan Boldogh ◽  
Nikola Vojtov ◽  
Sharon Karmon ◽  
Liza A. Pon
Keyword(s):  
Membrane Proteins ◽  
Actin Cytoskeleton ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Protein S ◽  
Binding Activity ◽  
Actin Binding ◽  
Mitochondrial Outer Membrane ◽  
Mitochondrial Movement ◽  
Mitochondrial Motility

Transfer of mitochondria to daughter cells during yeast cell division is essential for viable progeny. The actin cytoskeleton is required for this process, potentially as a track to direct mitochondrial movement into the bud. Sedimentation assays reveal two different components required for mitochondria–actin interactions: (1) mitochondrial actin binding protein(s) (mABP), a peripheral mitochondrial outer membrane protein(s) with ATP-sensitive actin binding activity, and (2) a salt-inextractable, presumably integral, membrane protein(s) required for docking of mABP on the organelle. mABP activity is abolished by treatment of mitochondria with high salt. Addition of either the salt-extracted mitochondrial peripheral membrane proteins (SE), or a protein fraction with ATP-sensitive actin-binding activity isolated from SE, to salt-washed mitochondria restores this activity. mABP docking activity is saturable, resistant to high salt, and inhibited by pre-treatment of salt-washed mitochondria with papain. Two integral mitochondrial outer membrane proteins, Mmm1p (Burgess, S.M., M. Delannoy, and R.E. Jensen. 1994. J.Cell Biol. 126:1375–1391) and Mdm10p, (Sogo, L.F., and M.P. Yaffe. 1994. J.Cell Biol. 126:1361– 1373) are required for these actin–mitochondria interactions. Mitochondria isolated from an mmm1-1 temperature-sensitive mutant or from an mdm10 deletion mutant show no mABP activity and no mABP docking activity. Consistent with this, mitochondrial motility in vivo in mmm1-1 and mdm10Δ mutants appears to be actin independent. Depolymerization of F-actin using latrunculin-A results in loss of long-distance, linear movement and a fivefold decrease in the velocity of mitochondrial movement. Mitochondrial motility in mmm1-1 and mdm10Δ mutants is indistinguishable from that in latrunculin-A–treated wild-type cells. We propose that Mmm1p and Mdm10p are required for docking of mABP on the surface of yeast mitochondria and coupling the organelle to the actin cytoskeleton.

scholarly journals The mitochondrial import protein Mim1 promotes biogenesis of multispanning outer membrane proteins

2011 ◽  
Vol 194 (3) ◽  
pp. 387-395 ◽  
Author(s):  
Thomas Becker ◽  
Lena-Sophie Wenz ◽  
Vivien Krüger ◽  
Waltraut Lehmann ◽  
Judith M. Müller ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane ◽  
Limited Information ◽  
Mitochondrial Import ◽  
Transmembrane Segments ◽  
Membrane Complex ◽  
Complex Functions ◽  
Precursor Proteins

The mitochondrial outer membrane contains translocase complexes for the import of precursor proteins. The translocase of the outer membrane complex functions as a general preprotein entry gate, whereas the sorting and assembly machinery complex mediates membrane insertion of β-barrel proteins of the outer membrane. Several α-helical outer membrane proteins are known to carry multiple transmembrane segments; however, only limited information is available on the biogenesis of these proteins. We report that mitochondria lacking the mitochondrial import protein 1 (Mim1) are impaired in the biogenesis of multispanning outer membrane proteins, whereas overexpression of Mim1 stimulates their import. The Mim1 complex cooperates with the receptor Tom70 in binding of precursor proteins and promotes their insertion and assembly into the outer membrane. We conclude that the Mim1 complex plays a central role in the import of α-helical outer membrane proteins with multiple transmembrane segments.

scholarly journals Saccharomyces cerevisiaePorin Pore Forms Complexes with Mitochondrial Outer Membrane Proteins Om14p and Om45p

2012 ◽  
Vol 287 (21) ◽  
pp. 17447-17458 ◽  
Author(s):  
Susann Lauffer ◽  
Katrin Mäbert ◽  
Cornelia Czupalla ◽  
Theresia Pursche ◽  
Bernard Hoflack ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Mitochondrial Outer Membrane
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