CLUH couples mitochondrial distribution to the energetic and metabolic status

• DOI: 10.1242/jcs.201616
• Publication Date: 2017-04-20T00:10:27Z
• Authors: Jamal Wakim; David Goudenege; Rodolphe Perrot; Naig Gueguen; Valerie Desquiret...; Juan Manuel Chao ...; Ilaria Dalla Rosa; Florence Manero; Morgane Le Mao; Stephanie Chupin; Arnaud Chevrollier; Vincent Procaccio; Dominique Bonneau; David C. Logan; Pascal Reynier; Guy Lenaers; Salim Khiati
• Keywords: Bioenergetics; Palmitoylcarnitine

Mitochondrial dynamics and distribution are critical for supplying ATP in response to energy demand. CLUH is a protein involved mitochondrial whose dysfunction leads clustering, the metabolic consequences of which remain unknown. To gain insight into role on production cellular metabolism, we have generated CLUH-knockout cells using CRISPR/Cas9. clustering was associated with smaller cell size decreased abundance respiratory complexes, resulting oxidative phosphorylation (OXPHOS) defects. This energetic impairment found be due alteration translation shift towards glucose dependency. Metabolomic profiling by mass spectroscopy revealed an increase concentration some amino acids, indicating dysfunctional Krebs cycle, increased palmitoylcarnitine concentration, fatty acid oxidation, dramatic decrease concentrations phosphatidylcholine sphingomyeline, consistent size. Taken together, our study establishes clear function coupling control status.