PMID- 27060253
OWN - NLM
STAT- MEDLINE
DCOM- 20160818
LR  - 20231213
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1857
IP  - 8
DP  - 2016 Aug
TI  - Clock-genes and mitochondrial respiratory activity: Evidence of a reciprocal 
      interplay.
PG  - 1344-1351
LID - S0005-2728(16)30083-4 [pii]
LID - 10.1016/j.bbabio.2016.03.035 [doi]
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.
FAU - Scrima, Rosella
AU  - Scrima R
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Cela, Olga
AU  - Cela O
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Merla, Giuseppe
AU  - Merla G
AD  - Medical Genetics Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni 
      Rotondo (FG), Italy.
FAU - Augello, Bartolomeo
AU  - Augello B
AD  - Medical Genetics Unit, IRCCS "Casa Sollievo della Sofferenza", San Giovanni 
      Rotondo (FG), Italy.
FAU - Rubino, Rosa
AU  - Rubino R
AD  - Molekulares Krebsforschungszentrum (MKFZ), Charite-Universitatsmedizin Berlin, 
      Germany; Institute for Theoretical Biology (ITB), Charite-Universitatsmedizin 
      Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Quarato, Giovanni
AU  - Quarato G
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Fugetto, Sabino
AU  - Fugetto S
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Menga, Marta
AU  - Menga M
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Fuhr, Luise
AU  - Fuhr L
AD  - Molekulares Krebsforschungszentrum (MKFZ), Charite-Universitatsmedizin Berlin, 
      Germany; Institute for Theoretical Biology (ITB), Charite-Universitatsmedizin 
      Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Relogio, Angela
AU  - Relogio A
AD  - Molekulares Krebsforschungszentrum (MKFZ), Charite-Universitatsmedizin Berlin, 
      Germany; Institute for Theoretical Biology (ITB), Charite-Universitatsmedizin 
      Berlin and Humboldt-Universitat zu Berlin, Berlin, Germany.
FAU - Piccoli, Claudia
AU  - Piccoli C
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy.
FAU - Mazzoccoli, Gianluigi
AU  - Mazzoccoli G
AD  - 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.
FAU - Capitanio, Nazzareno
AU  - Capitanio N
AD  - Department of Clinical and Experimental Medicine, University of Foggia, Foggia, 
      Italy. Electronic address: nazzareno.capitanio@unifg.it.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160407
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (ARNTL Transcription Factors)
RN  - 0 (BMAL1 protein, human)
RN  - 0 (DNA, Mitochondrial)
RN  - 0 (Oligomycins)
RN  - 0 (RNA, Small Interfering)
RN  - 03L9OT429T (Rotenone)
RN  - 370-86-5 (Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone)
RN  - 642-15-9 (Antimycin A)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - ARNTL Transcription Factors/antagonists & inhibitors/*genetics/metabolism
MH  - Antimycin A/pharmacology
MH  - Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone/pharmacology
MH  - Circadian Clocks/*genetics
MH  - DNA, Mitochondrial/genetics/metabolism
MH  - *Feedback, Physiological
MH  - Fibroblasts/cytology/drug effects/*metabolism
MH  - Gene Expression Regulation
MH  - Genes, Reporter
MH  - Genetic Vectors/chemistry/metabolism
MH  - Hep G2 Cells
MH  - Humans
MH  - Lentivirus/genetics
MH  - Luciferases/genetics/metabolism
MH  - Mitochondria/drug effects/*metabolism
MH  - Oligomycins/pharmacology
MH  - *Oxidative Phosphorylation
MH  - Primary Cell Culture
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Rotenone/pharmacology
MH  - Signal Transduction
OTO - NOTNLM
OT  - Clock-genes
OT  - Mitochondria
OT  - Oxidative phosphorylation
EDAT- 2016/04/10 06:00
MHDA- 2016/08/19 06:00
CRDT- 2016/04/10 06:00
PHST- 2015/12/15 00:00 [received]
PHST- 2016/03/25 00:00 [revised]
PHST- 2016/03/29 00:00 [accepted]
PHST- 2016/04/10 06:00 [entrez]
PHST- 2016/04/10 06:00 [pubmed]
PHST- 2016/08/19 06:00 [medline]
AID - S0005-2728(16)30083-4 [pii]
AID - 10.1016/j.bbabio.2016.03.035 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2016 Aug;1857(8):1344-1351. doi: 
      10.1016/j.bbabio.2016.03.035. Epub 2016 Apr 7.