Mitochondrial turnover in liver is fast in vivo and is accelerated by dietary restriction: application of a simple dynamic model.
'Mitochondrial dysfunction', which may result from an accumulation of damaged mitochondria in cells due to a slowed-down rate of mitochondrial turnover and inadequate removal of damaged mitochondria during aging, has been implicated as both cause and consequence of the aging process and a number of age-related pathologies. Despite growing interest in mitochondrial function during aging, published data on mitochondrial turnover are scarce, and differ from each other by up to one order of magnitude. Here we demonstrate that re-utilization of the radioactively labelled precursor in pulse-chase assays is the most likely cause of significant overestimation of mitochondrial turnover rates. We performed a classic radioactive label pulse-chase experiment using (14)C NaHCO(3), whose (14)C is incorporated into various amino acids, to measure mitochondrial turnover in mouse liver. In this system, the activity of the urea cycle greatly limited arginine dependent label re-utilization, but not that of other amino acids. We used information from tissues that do not have an active urea cycle (brain and muscle) to estimate the extent of label re-utilization with a dynamic mathematical model. We estimated the actual liver mitochondrial half life as only 1.83 days, and this decreased to 1.16 days following 3 months of dietary restriction, supporting the hypothesis that this intervention might promote mitochondrial turnover as a part of its beneficial effects.
Miwa
Satomi
S
Centre for Integrated Systems Biology of Ageing and Nutrition, Institute for Ageing and Health, Newcastle University, Newcastle upon Tyne, UK.
Lawless
Conor
C
von Zglinicki
Thomas
T
D000818:Animals; D002250:Carbon Radioisotopes; D005215:Fasting / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008110:Liver Extracts / Q000378:metabolism; D051379:Mice; D008930:Mitochondria, Liver / Q000378:metabolism*; D008954:Models, Biological
D002250:Carbon Radioisotopes; D008110:Liver Extracts