INSTITUTO DE QUIMICA, FISICA DE LOS MATERIALES, MEDIOAMBIENTE Y ENERGIA
Unidad Ejecutora - UE
Multifunctional cytochrome c: learning new tricks from an old dog
DANIEL H. MURGIDA; VERÓNICA TÓRTORA; MARIA ANA CASTRO; RAFAEL RADI; VERONICA DEMICHELI; FLORENCIA TOMASINA; LUCIANA HANNIBAL; SANTIAGO OVIEDO ROUCO; DAMIAN ALVAREZ-PAGGI
AMER CHEMICAL SOC
Lugar: Washington; Año: 2017 vol. 117 p. 13382 - 13382
Cytochrome c (cyt c) is a small soluble heme protein characterized by a relatively flexible structure, particularly in the ferric form, such that it is able to sample a broad conformational space. Depending on the specific conditions, interactions and cellular localization different conformations may be stabilized, which differ in structure, redox properties, binding affinities and enzymatic activity. The primary function is electron shuttling in oxidative phosphorylation, and is exerted by the so-called native cyt cin the intermembrane mitochondrial space of healthy cells. Under pro-apoptotic conditions, however, cyt c gains cardiolipin peroxidase activity, translocates into the cytosol to engage in the intrinsic apoptotic pathway and enters the nucleus where it impedes nucleosome assembly. Other reported functions include cytosolic redox sensing and involvement in the mitochondrial oxidative folding machinery. Moreover, post-translational modifications such as nitration, phosphorylation and sulfoxidation of specific amino acids induce alternative conformations with differential properties, at least in vitro. Similar structural and functional alterations are elicited by biologically significant electric fields and by naturally occurring mutations of human cyt cthat, along with mutations at the level of the maturation system, are associated with specific diseases.Here we summarize current knowledge and recent advances in understanding the different structural, dynamic and thermodynamic factors that regulate the primary electron transfer function, as well as alternative functions and conformations of cyt c.Finally, we present recent technological applications of this moonlighting protein.