Clock-genes and mitochondrial respiratory activity: Evidence of a reciprocal interplay

Rosella Scrima, Olga Cela, Giuseppe Merla, Bartolomeo Augello, Rosa Rubino, Giovanni Quarato, Sabino Fugetto, Marta Menga, Luise Fuhr, Angela Relógio, Claudia Piccoli, Gianluigi Mazzoccoli, Nazzareno Capitanio

Research output: Contribution to journalArticle

Abstract

In the past few years mounting evidences have highlighted the tight correlation between circadian rhythms and metabolism. Although at the organismal level the central timekeeper is constituted by the hypothalamic suprachiasmatic nuclei practically all the peripheral tissues are equipped with autonomous oscillators made up by common molecular clockworks represented by circuits of gene expression that are organized in interconnected positive and negative feed-back loops. In this study we exploited a well-established in vitro synchronization model to investigate specifically the linkage between clock gene expression and the mitochondrial oxidative phosphorylation (OxPhos). Here we show that synchronized cells exhibit an autonomous ultradian mitochondrial respiratory activity which is abrogated by silencing the master clock gene ARNTL/. BMAL1. Surprisingly, pharmacological inhibition of the mitochondrial OxPhos system resulted in dramatic deregulation of the rhythmic clock-gene expression and a similar result was attained with mtDNA depleted cells (Rho0). Our findings provide a novel level of complexity in the interlocked feedback loop controlling the interplay between cellular bioenergetics and the molecular clockwork. This article is part of a Special Issue entitled 'EBEC 2016: 19th European Bioenergetics Conference, Riva del Garda, Italy, July 2-6, 2016', edited by Prof. Paolo Bernardi.

Original languageEnglish
JournalBiochimica et Biophysica Acta - Bioenergetics
DOIs
Publication statusAccepted/In press - Dec 15 2015

Keywords

  • Clock-genes
  • Mitochondria
  • Oxidative phosphorylation

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Cell Biology

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  • Cite this

    Scrima, R., Cela, O., Merla, G., Augello, B., Rubino, R., Quarato, G., Fugetto, S., Menga, M., Fuhr, L., Relógio, A., Piccoli, C., Mazzoccoli, G., & Capitanio, N. (Accepted/In press). Clock-genes and mitochondrial respiratory activity: Evidence of a reciprocal interplay. Biochimica et Biophysica Acta - Bioenergetics. https://doi.org/10.1016/j.bbabio.2016.03.035