Ageing mitochondrial oxidative phosphorylation

A mutation in any of the 13 protein subunits, the 22 tRNAs, or the two rRNAs whose genes are carried in mitochondrial DNA may possibly cause disease. The 13 protein subunits are all involved in electron transport or oxidative phosphorylation. The syndromes resulting from mutations in mtDNA frequently affect oxidative phosphorylation (OXPHOS) causing what are often called "OXPHOS diseases."3-6 Mitochondrial oxidative phosphorylation also depends upon 100 proteins encoded in the nucleus. Therefore, OXPHOS diseases may result from defects in either mitochondrial or nuclear genes. The former are distinguished by the fact that they are inherited almost exclusively maternally. Most mitochondrial diseases are rare. However, mtDNA is subject to rapid mutation, and it is possible that accumulating mutants in mtDNA may be an important component of aging.h k... 

Studies in human skeletal muscle (Cooper et al. 1992, Boffoli etal. 1994), liver (Yen etal. 1989), and brain (Muller-HOcker etal. 1993) have revealed that mitochondrial oxidative phosphorylation declines during ageing. 

To gain further insight into the age-related adaptation of skeletal muscle to a more aerobic-oxidative metabolism, studying mitochondrial bioenergetic parameters and mitochondrial oxidative phosphorylation efficiency is of crucial importance. 

Recent development of mitochondrial theory of aging is so-called reductive hotspot hypothesis. De Grey [465] proposed that the cells with suppressed oxidative phosphorylation survive by reducing dioxygen at the plasma membrane rather than at the mitochondrial inner membrane. Plasma membrane redox system is apparently an origin of the conversion of superoxide into hydroxyl and peroxyl radicals and LDL oxidation. Morre et al. [466] suggested that plasma membrane oxidoreductase links the accumulation of lesions in mitochondrial DNA to the formation of reactive oxygen species on the cell surface. 

The first recognition of mitochondrial disease came in 1959. A 30-year old Swedish woman was found to have an extremely high basal metabolic rate (180% of normal), a high caloric intake (>3000 kcal / day), and an enormous perspiration rate. She had developed these symptoms at age seven. Examination of her mitochondria revealed that electron transport and oxidative phosphorylation were very loosely coupled. This explains the symptoms. However, the disease (Luft disease) is extremely rare and the underlying cause isn t known.1 Its recognition did focus attention on mitochondria, and by 1988,... 

Rat myocardium ultrastructurally differed more intensely between 3 and 6 than between 18 and 24 months of age (Welt etal. 2000). Lipid drops and mitochondrial degeneration were more prominent in the older rats. Ageing-related alterations were limited to interfibrillar mitochondria, while subsar-colemmal mitochondria remained unaffected (Fannin et al. 1999). Ageing decreased the rate of oxidative phosphorylation in interfibrillar mitochondria, including when stimulated by electron donors spe-... 

In this paper, we review some of our recent data on the proteomic profiles of ageing skeletal musele in the rats, with particular attention being paid to the mitochondrial protein profile and to the supramolecular organization of the mitochondrial respiratory chain. Proteomic profiles will then be related to mitochondrial functionality and to the efficiency of oxidative phosphorylation. In addition, in relation to the etiology of sarcopenia, we discuss possible interrelated roles among ROS production, mitochondrial efficiency, and the decline in the level of mitochondrial uncoupling protein-3 (UCP3). 

The age-related interactions between mitochondrial functioning and efficiency of respirasomes, feed efficiency and body composition remain to be investigated in farm animals. It should be also taken into account that despite the age-related decline in mitochondrial proton leak is a process that has positive effect in terms of the efficiency of oxidative phosphorylation, it could increase the... 

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