The C8ORF38 homologue Sicily is a cytosolic chaperone for a mitochondrial complex I subunit

Ke Zhang, Zhihong Li, Manish Jaiswal, Vafa Bayat, Bo Xiong, Hector Sandoval, Wu-Lin Charng, Gabriela David, Claire Haueter, Shinya Yamamoto, Brett H Graham, Hugo J Bellen

Research output: Contribution to journalArticlepeer-review

53 Scopus citations


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 neurodegeneration. Our data indicate that cytosolic chaperones are required for the subcellular transport of ND42.

Original languageEnglish (US)
Pages (from-to)807-20
Number of pages14
JournalJournal of Cell Biology
Issue number6
StatePublished - Mar 18 2013


  • Animals
  • Cell Line
  • Drosophila Proteins
  • Drosophila melanogaster
  • Electron Transport Complex I
  • Gene Deletion
  • HSP90 Heat-Shock Proteins
  • Humans
  • Leigh Disease
  • Mitochondria
  • Mitochondrial Proteins
  • Protein Transport
  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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