PT  - JOURNAL ARTICLE
AU  - Sara Palacios-Zambrano
AU  - Luis Vázquez-Fonseca
AU  - Cristina González-Páramos
AU  - Laura Mamblona
AU  - Laura Sánchez-Caballero
AU  - Leo Nijtmans
AU  - Rafael Garesse
AU  - Miguel Angel Fernández-Moreno
TI  - C6orf203 controls OXPHOS function through modulation of mitochondrial protein biosynthesis
AID  - 10.1101/704403
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 704403
4099  - http://biorxiv.org/content/early/2019/07/17/704403.short
4100  - http://biorxiv.org/content/early/2019/07/17/704403.full
AB  - Mitochondria are essential organelles present in the vast majority of eukaryotic cells. Their central function is to produce cellular energy through the OXPHOS system, and functional alterations provoke so-called mitochondrial OXPHOS diseases. It is estimated that several hundred mitochondrial proteins have unknown functions. Very recently, C6orf203 was described to participate in mitochondrial transcription under induced mitochondrial DNA depletion stress conditions. Here, we describe another role for C6orf203, specifically in OXPHOS biogenesis under regular culture conditions. HEK293T C6orf203-Knockout (KO) cells generated by CRISPR/Cas9 genome editing showed both reduced grow in galactose, as a carbon source, and in their oxygen consumption capability, strongly suggesting an OXPHOS dysfunction. C6orf203-KO also provoked a depletion of OXPHOS proteins and decreased the activity of the mitochondrial respiratory chain complexes. C6orf203 was present in high molecular weight complexes compatible with mitoribosomes, and in vivo labelling of de novo mitochondrial proteins synthesis revealed that C6orf203-KO severely but not completely affected the translation of mitochondrial mRNAs. Taken together, we describe herein a new function for C6orf203, making it a potential OXPHOS disease-related candidate.