Study of the regulation of mitochondrial oxidative phosphorylation in skeletal muscle

Mitochondria play a central role in energy production, meeting the specific needs of individual organs. Some organs, such as the heart, have no energy reserves and depend entirely on the continuous production of energy by the mitochondria. Others, like skeletal muscle, can store energy in the form of molecules such as phosphocreatine or ATP. These reserves make it possible to meet increased energy demands, particularly during physical exertion, when oxygen consumption (VO2) increases rapidly.

Energy production in the mitochondria relies on the respiratory chain, located in the inner membrane. This chain comprises several complexes (I to IV) and ATP synthase. Electrons, from reduced molecules such as NADH and FADH2, are transferred through these complexes. This transfer leads to the translocation of protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient. This gradient is crucial, as it is used by ATP synthase to produce ATP. The mechanism relies on the conversion of mechanical energy, derived from the rotation of a rotor, into chemical energy via the binding of a phosphate to ADP.

However, due to the imperfect permeability of the inner membrane, some protons return to the mitochondrial matrix without passing through ATP synthase. This leakage of protons from the inner membrane increases oxygen consumption without producing ATP. The researchers believe that this leakage phenomenon will be amplified during physical exertion. This leakage could also be influenced by the accumulation of certain metabolites which have an effect on membrane permeability, thus reducing overall energy efficiency by lowering the ratio between oxygen consumed and ATP produced (P/O ratio).

The aim of this internship is to gain a better understanding of this hypothesis. The first step will be to quantify this leakage using the P/O ratio on muscle fibers. Secondly, if an increase in leakage is confirmed, initial measurements to identify the metabolites involved in the increase in leakage will be carried out. For this, techniques such as oxygenography and muscle fiber permeability will be used.

#permeability # oxygenography #mitochondrialrespiration #energy #protonleakage #VO2

Study of the regulation of mitochondrial oxidative phosphorylation in skeletal muscle

Mitochondria play a central role in energy production, meeting the specific needs of individual organs. Some organs, such as the heart, have no energy reserves and depend entirely on the continuous production of energy by the mitochondria. Others, like skeletal muscle, can store energy in the form of molecules such as phosphocreatine or ATP. These reserves make it possible to meet increased energy demands, particularly during physical exertion, when oxygen consumption (VO2) increases rapidly.

Energy production in the mitochondria relies on the respiratory chain, located in the inner membrane. This chain comprises several complexes (I to IV) and ATP synthase. Electrons, from reduced molecules such as NADH and FADH2, are transferred through these complexes. This transfer leads to the translocation of protons from the mitochondrial matrix to the intermembrane space, creating a proton gradient. This gradient is crucial, as it is used by ATP synthase to produce ATP. The mechanism relies on the conversion of mechanical energy, derived from the rotation of a rotor, into chemical energy via the binding of a phosphate to ADP.

However, due to the imperfect permeability of the inner membrane, some protons return to the mitochondrial matrix without passing through ATP synthase. This leakage of protons from the inner membrane increases oxygen consumption without producing ATP. The researchers believe that this leakage phenomenon will be amplified during physical exertion. This leakage could also be influenced by the accumulation of certain metabolites which have an effect on membrane permeability, thus reducing overall energy efficiency by lowering the ratio between oxygen consumed and ATP produced (P/O ratio).

The aim of this internship is to gain a better understanding of this hypothesis. The first step will be to quantify this leakage using the P/O ratio on muscle fibers. Secondly, if an increase in leakage is confirmed, initial measurements to identify the metabolites involved in the increase in leakage will be carried out. For this, techniques such as oxygenography and muscle fiber permeability will be used.

#permeability # oxygenography #mitochondrialrespiration #energy #protonleakage #VO2

internship supervisor

Jérôme PIQUEREAU