Implication of mitochondria in muscular biology : a key role during early development, growth and muscular atrophy

Abstract

Mitochondria are implicated in the regulation of biological process controlling development, growth and muscle properties in farm animals, as well as sarcopenia during aging in humans. Recent results obtained at INRA on these aspects are reviewed in this paper.

First, the relationship between oxidative metabolism, mitochondria density and muscle contractile type is confirmed, and the specificity of mitochondria properties according to myosin isotypes is demonstrated. Contribution of mitochondria to the acquisition of muscle contractile types and to myoblast differentiation, through the mitochondria-nuclear cross-talk, is described, and the key roles of c-Myc, Calcineurine and myogenin in this process is clearly established. The involvement of the direct T3 mitochondrial pathway in the regulation of mitochondrial biogenesis and activity is confirmed both in vitro and in vivo.

No clear relation is found between mitochondrial activity and the amount of intramuscular fat, a key component of meat quality. In fact, muscle lipid content appears to be more related to intra-muscular adipocyte differentiation and lipid turnover rate than to any metabolic pathway.

We also show in pigs and chickens that uncoupling proteins, UCP2, UCP3 and avUCP are differentially regulated in the muscle, but it is still difficult to conclude on their physiological roles. UCP3 and avUCP are clearly implicated in the thermogenic effect of T3 and probably play a role in the control of basal metabolism, whereas avUCP can be seen as a key metabolic sensor in the chicken because its expression is modified by cold or warm exposure and correlated to the intensity of lipid metabolism.

Finally, mitochondrial H₂O₂;production increases during healthy aging but has no short-term effect on muscle aging (sarcopenia). In fact, accumulation of mitochondrial DNA deletions and alteration of the expression of mitochondrial or nuclear genes are only observed in very old patients (older than 80). However, sensitivity of mitochondrial respiration to calcium clearly increases with aging, a process that could contribute to the reduction of aged muscle resistance to stress and to the development of apoptosis.