TY - JOUR
T1 - The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial complex i subunit
AU - Zhang, Ke
AU - Li, Zhihong
AU - Jaiswal, Manish
AU - Bayat, Vafa
AU - Xiong, Bo
AU - Sandoval, Hector
AU - Charng, Wu Lin
AU - David, Gabriela
AU - Haueter, Claire
AU - Yamamoto, Shinya
AU - Graham, Brett H.
AU - Bellen, Hugo J.
PY - 2013/3
Y1 - 2013/3
N2 - Mitochondrial complex I (CI) is an essential component in energy production through oxidative phosphorylation. Most CI subunits are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria. Upon entry, they are embedded into the mitochondrial inner membrane. How these membrane-associated proteins cope with the hydrophilic cytoplasmic environment before import is unknown. In a forward genetic screen to identify genes that cause neurodegeneration, we identified sicily, the Drosophila melanogaster homologue of human C8ORF38, the loss of which causes Leigh syndrome. We show that in the cytoplasm, Sicily preprotein interacts with cytosolic Hsp90 to chaperone the CI subunit, ND42, before mitochondrial import. Loss of Sicily leads to loss of CI proteins and preproteins in both mitochondria and cytoplasm, respectively, and causes a CI deficiency and neuro-degeneration. Our data indicate that cytosolic chaper-ones are required for the subcellular transport of ND42.
AB - Mitochondrial complex I (CI) is an essential component in energy production through oxidative phosphorylation. Most CI subunits are encoded by nuclear genes, translated in the cytoplasm, and imported into mitochondria. Upon entry, they are embedded into the mitochondrial inner membrane. How these membrane-associated proteins cope with the hydrophilic cytoplasmic environment before import is unknown. In a forward genetic screen to identify genes that cause neurodegeneration, we identified sicily, the Drosophila melanogaster homologue of human C8ORF38, the loss of which causes Leigh syndrome. We show that in the cytoplasm, Sicily preprotein interacts with cytosolic Hsp90 to chaperone the CI subunit, ND42, before mitochondrial import. Loss of Sicily leads to loss of CI proteins and preproteins in both mitochondria and cytoplasm, respectively, and causes a CI deficiency and neuro-degeneration. Our data indicate that cytosolic chaper-ones are required for the subcellular transport of ND42.
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U2 - 10.1083/jcb.201208033
DO - 10.1083/jcb.201208033
M3 - Article
C2 - 23509070
AN - SCOPUS:84876342142
SN - 0021-9525
VL - 200
SP - 807
EP - 820
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -