Clock genes-dependent acetylation of complex I sets rhythmic activity of mitochondrial OxPhos

Abstract

Physiology of living beings show circadian rhythms entrained by a central timekeeper present in the hypothalamic suprachiasmatic nuclei. Nevertheless, virtually all peripheral tissues hold autonomous molecular oscillators constituted essentially by circuits of gene expression that are organized in negative and positive feed-back loops. Accumulating evidence reveals that cell metabolism is rhythmically controlled by cell-intrinsic molecular clocks and the specific pathways involved are being elucidated. Here, we show that in vitro-synchronized cultured cells exhibit BMAL1-dependent oscillation in mitochondrial respiratory activity, which occurs irrespective of the cell type tested, the protocol of synchronization used and the carbon source in the medium. We demonstrate that the rhythmic respiratory activity is associated to oscillation in cellular NAD content and clock-genes-dependent expression of NAMPT and Sirtuins 1/3 and is traceable back to the reversible acetylation of a single subunit of the mitochondrial respiratory chain Complex I. Our findings provide evidence for a new interlocked transcriptional-enzymatic feedback loop controlling the molecular interplay between cellular bioenergetics and the molecular clockwork.


Autore Pugliese

Tutti gli autori

  • Cela O. , Scrima R. , Pazienza V. , Merla G. , Benegiamo G. , Augello B. , Fugetto S. , Menga M. , Rubino R. , Fuhr L. , Relógio A. , Piccoli C. , Mazzoccoli G. , Capitanio N.

Titolo volume/Rivista

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH


Anno di pubblicazione

2016

ISSN

0167-4889

ISBN

Non Disponibile


Numero di citazioni Wos

Nessuna citazione

Ultimo Aggiornamento Citazioni

Non Disponibile


Numero di citazioni Scopus

6

Ultimo Aggiornamento Citazioni

Non Disponibile


Settori ERC

Non Disponibile

Codici ASJC

Non Disponibile