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 language | English |
|---|---|
| Journal | Biochimica et Biophysica Acta - Bioenergetics |
| DOIs | |
| Publication status | Accepted/In press - Dec 15 2015 |
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Keywords
- Clock-genes
- Mitochondria
- Oxidative phosphorylation
ASJC Scopus subject areas
- Biochemistry
- Biophysics
- Cell Biology
Cite this
Clock-genes and mitochondrial respiratory activity : Evidence of a reciprocal interplay. / Scrima, Rosella; Cela, Olga; Merla, Giuseppe; Augello, Bartolomeo; Rubino, Rosa; Quarato, Giovanni; Fugetto, Sabino; Menga, Marta; Fuhr, Luise; Relógio, Angela; Piccoli, Claudia; Mazzoccoli, Gianluigi; Capitanio, Nazzareno.
In: Biochimica et Biophysica Acta - Bioenergetics, 15.12.2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clock-genes and mitochondrial respiratory activity
T2 - Evidence of a reciprocal interplay
AU - Scrima, Rosella
AU - Cela, Olga
AU - Merla, Giuseppe
AU - Augello, Bartolomeo
AU - Rubino, Rosa
AU - Quarato, Giovanni
AU - Fugetto, Sabino
AU - Menga, Marta
AU - Fuhr, Luise
AU - Relógio, Angela
AU - Piccoli, Claudia
AU - Mazzoccoli, Gianluigi
AU - Capitanio, Nazzareno
PY - 2015/12/15
Y1 - 2015/12/15
N2 - 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.
AB - 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.
KW - Clock-genes
KW - Mitochondria
KW - Oxidative phosphorylation
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UR - http://www.scopus.com/inward/citedby.url?scp=84963579212&partnerID=8YFLogxK
U2 - 10.1016/j.bbabio.2016.03.035
DO - 10.1016/j.bbabio.2016.03.035
M3 - Article
JO - Biochimica et Biophysica Acta - Bioenergetics
JF - Biochimica et Biophysica Acta - Bioenergetics
SN - 0005-2728
ER -