Parvalbumin deficiency in fast-twitch muscles leads to increased 'slow-twitch type' mitochondria, but does not affect the expression of fiber specific proteins.
Parvalbumin (PV), a small cytosolic protein belonging to the family of EF-hand calcium-binding proteins, is highly expressed in mammalian fast-twitch muscle fibers. By acting as a 'slow-onset' Ca2+ buffer, PV does not affect the rapid contraction phase, but significantly contributes to increase the rate of relaxation, as demonstrated in PV-/- mice. Unexpectedly, PV-/- fast-twitch muscles were considerably more resistant to fatigue than the wild-type fast-twitch muscles. This effect was attributed mainly to the increased fractional volume of mitochondria in PV-/- fast-twitch muscle, extensor digitorum longus, similar to levels observed in the slow-twitch muscle, soleus. Quantitative analysis of selected mitochondrial proteins, mitochondrial DNA-encoded cytochrome oxidase c subunit I and nuclear DNA-encoded cytochrome oxidase c subunit Vb and F1-ATPase subunit beta revealed the PV-/- tibialis anterior mitochondria composition to be almost identical to that in wild-type soleus, but not in wild-type fast-twitch muscles. Northern and western blot analyses of the same proteins in different muscle types and in liver are indicative of a complex regulation, probably also at the post-transcriptional level. Besides the function in energy metabolism, mitochondria in both fast- and slow-twitch muscles act as temporary Ca2+ stores and are thus involved in the shaping of Ca2+ transients in these cells. Previously observed altered spatio-temporal aspects of Ca2+ transients in PV-/- muscles are sufficient to up-regulate mitochondria biogenesis through the probable involvement of both calcineurin- and Ca2+/calmodulin-dependent kinase II-dependent pathways. We propose that 'slow-twitch type' mitochondria in PV-/- fast muscles are aimed to functionally replace the slow-onset buffer PV based on similar kinetic properties of Ca2+ removal.
Racay
Peter
P
Department of Medicine, Division of Histology and General Embryology, University of Fribourg, Switzerland.
Gregory
Patrick
P
Schwaller
Beat
B
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D015180:Electrophoresis, Gel, Two-Dimensional; D007150:Immunohistochemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018656:Muscle Fibers, Fast-Twitch / Q000378:metabolism* / Q000648:ultrastructure; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism* / Q000648:ultrastructure; D009124:Muscle Proteins / Q000378:metabolism*; D010320:Parvalbumins / Q000378:metabolism / Q000502:physiology*
D024101:Mitochondrial Proteins; D009124:Muscle Proteins; D010320:Parvalbumins; D000255:Adenosine Triphosphate; D002118:Calcium