Biochemistry of Mitochondrial Coenzyme Q Biosynthesis

Jonathan A. Stefely, David J. Pagliarini

Research output: Contribution to journalReview articlepeer-review

94 Scopus citations

Abstract

Coenzyme Q (CoQ, ubiquinone) is a redox-active lipid produced across all domains of life that functions in electron transport and oxidative phosphorylation and whose deficiency causes human diseases. Yet, CoQ biosynthesis has not been fully defined in any organism. Several proteins with unclear molecular functions facilitate CoQ biosynthesis through unknown means, and multiple steps in the pathway are catalyzed by currently unidentified enzymes. Here we highlight recent progress toward filling these knowledge gaps through both traditional biochemistry and cutting-edge ‘omics’ approaches. To help fill the remaining gaps, we present questions framed by the recently discovered CoQ biosynthetic complex and by putative biophysical barriers. Mapping CoQ biosynthesis, metabolism, and transport pathways has great potential to enhance treatment of numerous human diseases. A biosynthetic complex for producing CoQ was recently revealed in yeast and mammals. This complex likely contains proteins, lipids, and polar small molecules, but its precise composition, structure, and activities remain largely unknown. Multiple MXPs have been linked to CoQ biosynthesis, and multiple steps in the pathway are enabled by currently unidentified proteins. Recent progress was made toward understanding the biochemistry of a dehydrogenase, a deaminase, a lipid-binding protein, and a protein kinase-like enzyme in the CoQ pathway. CoQ biosynthesis spans multiple ‘omic’ planes – the metabolome, the lipidome, and the proteome – and thus has proven to be a prime target for investigation with emerging multiomic technologies. Mapping CoQ biochemistry recently spurred new therapeutic strategies.

Original languageEnglish
Pages (from-to)824-843
Number of pages20
JournalTrends in biochemical sciences
Volume42
Issue number10
DOIs
StatePublished - Oct 2017

Keywords

  • CoQ-synthome
  • biosynthesis
  • coenzyme Q
  • complex Q
  • lipids
  • metabolon
  • mitochondria
  • mitochondrial disease
  • oxidative phosphorylation
  • protein complex
  • ubiquinone

Fingerprint

Dive into the research topics of 'Biochemistry of Mitochondrial Coenzyme Q Biosynthesis'. Together they form a unique fingerprint.

Cite this