| RRC ID |
46193
|
| Author |
Shen Q, Yamano K, Head BP, Kawajiri S, Cheung JT, Wang C, Cho JH, Hattori N, Youle RJ, van der Bliek AM.
|
| Title |
Mutations in Fis1 disrupt orderly disposal of defective mitochondria.
|
| Journal |
Mol Biol Cell
|
| Abstract |
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.
|
| Volume |
25(1)
|
| Pages |
145-59
|
| Published |
2014-1-1
|
| DOI |
10.1091/mbc.E13-09-0525
|
| PII |
mbc.E13-09-0525
|
| PMID |
24196833
|
| PMC |
PMC3873885
|
| MeSH |
Animals
Caenorhabditis elegans / cytology
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism*
Caenorhabditis elegans Proteins / genetics*
Caenorhabditis elegans Proteins / metabolism
Endoplasmic Reticulum / metabolism
HCT116 Cells
HeLa Cells
Humans
Membrane Proteins / genetics*
Membrane Proteins / metabolism
Microtubule-Associated Proteins / metabolism
Mitochondrial Dynamics*
Mitochondrial Proteins / genetics*
Mitochondrial Proteins / metabolism
Muscles / cytology
Mutation, Missense
Proteolysis
|
| IF |
3.791
|
| Times Cited |
98
|
|
WOS Category
|
CELL BIOLOGY
|
| Resource |
| C.elegans |
tm1867
tm2955
tm3041
tm1108
tm1779
tm1861
tm1799 |
