TY - JOUR
T1 - MICOS subcomplexes assemble independently on the mitochondrial inner membrane in proximity to ER contact sites
AU - Tirrell, Parker S.
AU - Nguyen, Kailey N.
AU - Luby-Phelps, Katherine
AU - Friedman, Jonathan R.
N1 - Funding Information:
The UT Southwestern Live Cell Imaging Facility, which is supported in part by National Institutes of Health grant P30CA142543, provided access to the Zeiss LSM880/Airyscan microscope (purchased with National Institutes of Health grant 1S10OD021684-01 to KLP) and deconvolution software. J.R. Friedman is supported by funding from the National Institutes of Health (R00HL133372 and R35GM137894) and the Welch Foundation (I-1951-20180324). The authors declare no competing financial interests.
Publisher Copyright:
© 2020 Tirrell et al.
PY - 2020/10/7
Y1 - 2020/10/7
N2 - MICOS is a conserved multisubunit complex that localizes to mitochondrial cristae junctions and organizes cristae positioning within the organelle. MICOS is organized into two independent subcomplexes; however, the mechanisms that dictate the assembly and spatial positioning of each MICOS subcomplex are poorly understood. Here, we determine that MICOS subcomplexes target independently of one another to sites on the inner mitochondrial membrane that are in proximity to contact sites between mitochondria and the ER. One subcomplex, composed of Mic27/Mic26/Mic10/Mic12, requires ERMES complex function for its assembly. In contrast, the principal MICOS component, Mic60, self-assembles and localizes in close proximity to the ER through an independent mechanism. We also find that Mic60 can uniquely redistribute adjacent to forced mitochondria-vacuole contact sites. Our data suggest that nonoverlapping properties of interorganelle contact sites provide spatial cues that enable MICOS assembly and ultimately lead to proper physical and functional organization of mitochondria.
AB - MICOS is a conserved multisubunit complex that localizes to mitochondrial cristae junctions and organizes cristae positioning within the organelle. MICOS is organized into two independent subcomplexes; however, the mechanisms that dictate the assembly and spatial positioning of each MICOS subcomplex are poorly understood. Here, we determine that MICOS subcomplexes target independently of one another to sites on the inner mitochondrial membrane that are in proximity to contact sites between mitochondria and the ER. One subcomplex, composed of Mic27/Mic26/Mic10/Mic12, requires ERMES complex function for its assembly. In contrast, the principal MICOS component, Mic60, self-assembles and localizes in close proximity to the ER through an independent mechanism. We also find that Mic60 can uniquely redistribute adjacent to forced mitochondria-vacuole contact sites. Our data suggest that nonoverlapping properties of interorganelle contact sites provide spatial cues that enable MICOS assembly and ultimately lead to proper physical and functional organization of mitochondria.
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U2 - 10.1083/JCB.202003024
DO - 10.1083/JCB.202003024
M3 - Article
C2 - 33053165
AN - SCOPUS:85092885976
SN - 0021-9525
VL - 219
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 11
M1 - e202003024
ER -