December 2012

Tiny mitochondrial intermembrane space’s proteome

Cover of the December 2012 issue of the journal Molecular & Cellular Proteomics

Despite being the smallest of the four mitochondrial compartments, the intermembrane space is important for several of the organelle’s functions. Among other things, the IMS oversees the transport and modification of proteins and other entities, regulates the respiratory chain complexes and coordinates apoptosis. But not many details are known about the compartment.

In a recent Molecular & Cellular Proteomics paper (1), a team led by René P. Zahedi at the Leibniz Institute for Analytical Sciences and Chris Meisinger at the Albert-Ludwig University of Freiburg (both in Germany) did the first IMS proteomic profile in yeast (1).

Because there wasn’t a straightforward way to purify IMS proteins from those in the other three mitochondrial compartments, “we developed a dedicated strategy that utilizes recombinant mammalian Bax, one of the key components to trigger apoptosis in mammalian cells,” explains Meisinger. Bax inserts into the outer mitochondrial membrane to release cytochrome C and most of the soluble IMS proteins. So Meisinger, Zahedi and colleagues exploited this conserved biochemical mechanism to trigger the release of IMS proteins and analyze them by quantitative mass spectrometry.

The investigators identified 49 proteins, of which 20 were novel. Ten of the 20 “had not even been localized to mitochondria before,” says Meisinger. The investigators discovered a novel assembly factor for respiratory complex IV, which had been annotated as a protein of unknown function and localization. The investigators call it Coa6. “Another surprise was the identification of thioredoxins and thioredoxin reductases,” says Meisinger. “The IMS was thought to provide an oxidative environment. However, these enzymes seem to also provide reductive capacity.”

  1. 1. Vögtle, F.-N. et al. Mol. Cell. Proteomics (2012) DOI: 10.1074/mcp.M112.021105.

Raj_MukhopadhyayRajendrani Mukhopadhyay ( is the senior science writer for ASBMB Today and the technical editor for The Journal of Biological Chemistry. Follow her on Twitter (

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