Clock genes-dependent acetylation of complex I sets rhythmic activity of mitochondrial OxPhos

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

Research output: Contribution to journalArticlepeer-review


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 BMAL1-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.

Original languageEnglish
Pages (from-to)596-606
Number of pages11
JournalBiochimica et Biophysica Acta - Molecular Cell Research
Issue number4
Publication statusPublished - Apr 1 2016


  • Clock-genes
  • Complex I
  • Mitochondria
  • NAD
  • Oxidative phosphorylation
  • Sirtuins

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology


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