English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

MITRAC7 defines a checkpoint during cytochrome c oxidase assembly.

MPS-Authors
/persons/resource/persons45937

Jans,  D. C.
Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society;

/persons/resource/persons15269

Jakobs,  S.
Research Group of Mitochondrial Structure and Dynamics, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

2183354.pdf
(Publisher version), 4MB

Supplementary Material (public)

2183354_Suppl_1.pdf
(Supplementary material), 10MB

2183354_Suppl_2.pdf
(Supplementary material), 13MB

Citation

Dennerlein, S., Oeljeklaus, S., Jans, D. C., Hellwig, C., Bareth, B., Jakobs, S., et al. (2015). MITRAC7 defines a checkpoint during cytochrome c oxidase assembly. Cell Reports, 12(10), 1644-1655. doi:10.1016/j.celrep.2015.08.009.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-466E-C
Abstract
Cytochrome c oxidase, the terminal enzyme of the respiratory chain, is assembled from mitochondria- and nuclear-encoded subunits. The MITRAC complex represents the central assembly intermediate during this process as it receives imported subunits and regulates mitochondrial translation of COX1 mRNA. The molecular processes that promote and regulate the progression of assembly downstream of MITRAC are still unknown. Here, we identify MITRAC7 as a constituent of a late form of MITRAC and as a COX1-specific chaperone. MITRAC7 is required for cytochrome c oxidase biogenesis. Surprisingly, loss of MITRAC7 or an increase in its amount causes selective cytochrome c oxidase deficiency in human cells. We demonstrate that increased MITRAC7 levels stabilize and trap COX1 in MITRAC, blocking progression in the assembly process. In contrast, MITRAC7 deficiency leads to turnover of newly synthesized COX1. Accordingly, MITRAC7 affects the biogenesis pathway by stabilizing newly synthesized COX1 in assembly intermediates, concomitantly preventing turnover.