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Biochim Biophys Acta. 2016 Aug;1857(8):1344-1351. doi: 10.1016/j.bbabio.2016.03.035. Epub 2016 Apr 7.

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

Author information

1
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy.
2
Medical Genetics Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy.
3
Molekulares Krebsforschungszentrum (MKFZ), Charité-Universitätsmedizin Berlin, Germany; Institute for Theoretical Biology (ITB), Charité-Universitätsmedizin Berlin and Humboldt-Universität zu Berlin, Berlin, Germany.
4
Department of Medical Sciences, Division of Internal Medicine and Chronobiology Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni Rotondo (FG), Italy. Electronic address: g.mazzoccoli@operapadrepio.it.
5
Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy. Electronic address: nazzareno.capitanio@unifg.it.

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.

KEYWORDS:

Clock-genes; Mitochondria; Oxidative phosphorylation

PMID:
27060253
DOI:
10.1016/j.bbabio.2016.03.035
[Indexed for MEDLINE]
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