The relationship between mitochondria function and circadian clock in peripheral oscillators

• Autorzy: Kazmierczak A. , Schmitt K. , Grimm A. , Strosznajder J. B. , Eckert A.
• Języki publikacji: EN

Abstrakty

EN

Circadian rhythms govern a wide variety of physical, behavioral and metabolic changes that follow a roughly 24-hour cycle, responding primarily to light and darkness in an organism’s environment. These are controlled by the circadian clock mechanism, where rhythm-generating mechanism is encoded by a transcription-translation feedback loop. Numerous studies have pointed to a cyclic relationship wherein the rhythm impacts metabolic activity and metabolism feeds back to impinge upon the rhythm. Mitochondria play a pivotal role in regulating cellular energy and were shown to be strategically positioned at the intersection between circadian rhythm and cell metabolism. Nevertheless little is known about their function in controlling the circadian rhythm. In our study, we investigated the involvement of circadian clock in mitochondrial function as well as mitochondria-dependent regulation of circadian clock. The study was carried out in primary human fibroblasts, an already established model to investigate molecular clock mechanisms in vitro. We have found that mitochondria activity as well as network activities showed rhythmic changes within 24 hours. Circadian pattern was detected for mitochondrial ROS including superoxide anion production. A significant 24-hour oscillation was found for cellular redox state. Furthermore, mitochondrial ATP levels were rhythmic and the maximum of ATP production paralleled the peak of mitochondrial ROS level and the mitochondrial network formation. Circadian rhythm was also detected for calcium ions concentration. Increase of ATP synthesis as well as changes in calcium and ROS level activated AMP-dependent protein kinase (AMPK). We have found that in primary human fibroblasts AMPK protein level and activity fluctuate in an antiphase relationship with rhythmic ATP production. Summarizing, our data provide the evidence for circadian regulation of mitochondrial dynamics and suggest that changes of mitochondrial activity may directly influence cellular clock. Supported by grants from Sciex 10. 258 to A.K. as well as Swiss National foundation (SNF No 310030_122572) and Synapsis Foundation to A.E

Słowa kluczowe

EN

relationship; mitochondrial function; circadian clock; circadian rhythm; 24-hour cycle; light; darkness; peripheral oscillator; cellular metabolism; cellular clock

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2013
• Tom: 73
• Numer: 1
• Opis fizyczny: p.188

Twórcy

autor

Kazmierczak A.

• Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland

autor

Schmitt K.

• Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland

autor

Grimm A.

• Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland

autor

Strosznajder J. B.

• Department of Cellular Signaling, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland

autor

Eckert A.

• Neurobiology Laboratory for Brain Aging and Mental Health, Psychiatric University Clinics, University of Basel, Basel, Switzerland