bims-cytox1 Biomed News
on Cytochrome oxidase subunit 1
Issue of 2017‒12‒10
two papers selected by
Gavin McStay
New York Institute of Technology

  1. Cell Chem Biol. 2017 Nov 24. pii: S2451-9456(17)30396-3. [Epub ahead of print]
      Human COQ8A (ADCK3) and Saccharomyces cerevisiae Coq8p (collectively COQ8) are UbiB family proteins essential for mitochondrial coenzyme Q (CoQ) biosynthesis. However, the biochemical activity of COQ8 and its direct role in CoQ production remain unclear, in part due to lack of known endogenous regulators of COQ8 function and of effective small molecules for probing its activity in vivo. Here, we demonstrate that COQ8 possesses evolutionarily conserved ATPase activity that is activated by binding to membranes containing cardiolipin and by phenolic compounds that resemble CoQ pathway intermediates. We further create an analog-sensitive version of Coq8p and reveal that acute chemical inhibition of its endogenous activity in yeast is sufficient to cause respiratory deficiency concomitant with CoQ depletion. Collectively, this work defines lipid and small-molecule modulators of an ancient family of atypical kinase-like proteins and establishes a chemical genetic system for further exploring the mechanistic role of COQ8 in CoQ biosynthesis.
    Keywords:  2-alkylphenols; ATPase; COQ8A; Coq8p; UbiB; analog-sensitive; atypical kinase; cardiolipin; coenzyme Q; mitochondrial chemical biology
  2. Cell Syst. 2017 Nov 24. pii: S2405-4712(17)30487-8. [Epub ahead of print]
      While modern structural biology technologies have greatly expanded the size and type of protein complexes that can now be studied, the ability to derive large-scale structural information on proteins and complexes as they exist within tissues is practically nonexistent. Here, we demonstrate the application of crosslinking mass spectrometry to identify protein structural features and interactions in tissue samples, providing systems structural biology insight into protein complexes as they exist in the mouse heart. This includes insights into multiple conformational states of sarcomere proteins, as well as interactions among OXPHOS complexes indicative of supercomplex assembly. The extension of crosslinking mass spectrometry analysis into the realm of tissues opens the door to increasing our understanding of protein structures and interactions within the context of the greater biological system.
    Keywords:  crosslinking; heart tissue; interactome; mass spectrometry; mitochondria; protein interactions; respiration; sarcomere; supercomplex; systems structural biology