The role of mitochondrial porins and the permeability transition pore in learning and synaptic plasticity.

Mitochondrial outer membrane permeability is conferred by a family of porin proteins. Mitochondrial porins conduct small molecules and constitute one component of the permeability transition pore that opens in response to apoptotic signals. Because mitochondrial porins have significant roles in diverse cellular processes including regulation of mitochondrial ATP and calcium flux, we sought to determine their importance in learning and synaptic plasticity in mice.

Altered mitochondrial sensitivity for ADP and maintenance of creatine-stimulated respiration in oxidative striated muscles from VDAC1-deficient mice.

Voltage-dependent anion channels (VDACs) form the main pathway for metabolites across the mitochondrial outer membrane. The mouse vdac1 gene has been disrupted by gene targeting, and the resulting mutant mice have been examined for defects in muscle physiology. To test the hypothesis that VDAC1 constitutes a pathway for ADP translocation into mitochondria, the apparent mitochondrial sensitivity for ADP (Km(ADP)) and the calculated rate of respiration in the presence of the maximal ADP concentration (Vmax) have been assessed using skinned fibers prepared from two oxidative muscles (ventricle and soleus) and a glycolytic muscle (gastrocnemius) in control and vdac1(-/-) mice.

Muscle unloading induces slow to fast transitions in myofibrillar but not mitochondrial properties. Relevance to skeletal muscle abnormalities in heart failure.

Muscle deconditioning is a common observation in patients with congestive heart failure (CHF), chronic obstructive pulmonary disease, neuromuscular diseases or prolonged bed rest. To gain further insight into metabolic and mechanical properties of deconditioned slow-twitch (soleus) or fast-twitch (EDL) skeletal muscles, we induced experimental muscle deconditioning by hindlimb suspension (HS) in rats for 3 weeks. Cardiac muscle was also studied.

Functional coupling of creatine kinases in muscles: species and tissue specificity.

Creatine kinase (CK) isoenzymes are present in all vertebrates. An important property of the creatine kinase system is that its total activity, its isoform distribution, and the concentration of guanidino substrates are highly variable among species and tissues. In the highly organized structure of adult muscles, it has been shown that specific CK isoenzymes are bound to intracellular compartments, and are functionally coupled to enzymes and transport systems involved in energy production and utilization.

Characterization of rat porin isoforms: cloning of a cardiac type-3 variant encoding an additional methionine at its putative N-terminal region.

In vivo, the outer mitochondrial membrane presents a restriction of diffusion for ADP in heart and slow twitch skeletal muscles, but not in fast twitch skeletal muscle. Mitochondrial porins constitute the main pathway for the transit of metabolites across the outer mitochondrial membrane. We decided, therefore, to characterize, by cloning, rat heart VDAC and to follow their expression in different striated muscles.