期刊
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
卷 1863, 期 4, 页码 596-606出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbamcr.2015.12.018
关键词
Mitochondria; Clock-genes; Oxidative phosphorylation; Complex I; NAD; Sirtuins
资金
- University of Foggia through the Department of Clinical and Experimental Medicine
- Italian Ministry of Health through Division of Internal Medicine and Chronobiology Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo (FG), Italy [RC1203ME46, RC1302ME31, RC1403ME50, RC1504ME53]
- German Federal Ministry of Education and Research (BMBF)-eBio-CIRSPLICE [FKZ031A316]
- Berlin School of Integrative Oncology (BSIO) of the Charite Universitatsmedizin Berlin
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 BMALl-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. (C) 2015 Elsevier B.V. All rights reserved.
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