Zc3h10 is a novel mitochondrial regulator

M. Audano, S. Pedretti, G. Cermenati, E. Brioschi, G.R. Diaferia, S. Ghisletti, A. Cuomo, T. Bonaldi, F. Salerno, M. Mora, L. Grigore, K. Garlaschelli, A. Baragetti, F. Bonacina, A.L. Catapano, G.D. Norata, M. Crestani, D. Caruso, E. Saez, E. De FabianiN. Mitro

Research output: Contribution to journalArticlepeer-review

Abstract

Mitochondria are the energy-generating hubs of the cell. In spite of considerable advances, our understanding of the factors that regulate the molecular circuits that govern mitochondrial function remains incomplete. Using a genome-wide functional screen, we identify the poorly characterized protein Zinc finger CCCH-type containing 10 (Zc3h10) as regulator of mitochondrial physiology. We show that Zc3h10 is upregulated during physiological mitochondriogenesis as it occurs during the differentiation of myoblasts into myotubes. Zc3h10 overexpression boosts mitochondrial function and promotes myoblast differentiation, while the depletion of Zc3h10 results in impaired myoblast differentiation, mitochondrial dysfunction, reduced expression of electron transport chain (ETC) subunits, and blunted TCA cycle flux. Notably, we have identified a loss-of-function mutation of Zc3h10 in humans (Tyr105 to Cys105) that is associated with increased body mass index, fat mass, fasting glucose, and triglycerides. Isolated peripheral blood mononuclear cells from individuals homozygotic for Cys105 display reduced oxygen consumption rate, diminished expression of some ETC subunits, and decreased levels of some TCA cycle metabolites, which all together derive in mitochondrial dysfunction. Taken together, our study identifies Zc3h10 as a novel mitochondrial regulator. © 2018 The Authors
Original languageEnglish
JournalEMBO Reports
Volume19
Issue number4
Publication statusPublished - 2018

Keywords

  • functional screens
  • metabolism
  • mitochondria
  • Zc3h10
  • genomic DNA
  • glucose
  • regulator protein
  • triacylglycerol
  • unclassified drug
  • Zinc finger CCCH type containing 10
  • aged
  • animal experiment
  • animal tissue
  • Article
  • body mass
  • cell differentiation
  • cell isolation
  • citric acid cycle
  • controlled study
  • embryo
  • fat mass
  • female
  • gene overexpression
  • glucose blood level
  • homozygote
  • human
  • human cell
  • human tissue
  • loss of function mutation
  • male
  • mitochondrial biogenesis
  • mitochondrion
  • mouse
  • myoblast
  • myotube
  • nonhuman
  • oxygen consumption
  • peripheral blood mononuclear cell
  • priority journal
  • protein depletion
  • protein expression
  • protein function
  • protein subunit
  • respiratory chain
  • triacylglycerol blood level
  • upregulation

Fingerprint Dive into the research topics of 'Zc3h10 is a novel mitochondrial regulator'. Together they form a unique fingerprint.

Cite this