title: Alternative Conformations of Cytochrome c: Structure, Function, and Detection.
abstract: Cytochrome c (cyt c) is a cationic hemoprotein of ∼100 amino acid residues that exhibits exceptional functional versatility. While its primary function is electron transfer in the respiratory chain, cyt c is also recognized as a key component of the intrinsic apoptotic pathway, the mitochondrial oxidative protein folding machinery, and presumably as a redox sensor in the cytosol, along with other reported functions. Transition to alternative conformations and gain-of-peroxidase activity are thought to further enable the multiple functions of cyt c and its translocation across cellular compartments. In vitro, direct interactions of cyt c with cardiolipin, post-translational modifications such as tyrosine nitration, phosphorylation, methionine sulfoxidation, mutations, and even fine changes in electrical fields lead to a variety of conformational states that may be of biological relevance. The identification of these alternative conformations and the elucidation of their functions in vivo continue to be a major challenge. Here, we unify the knowledge of the structural flexibility of cyt c that supports functional moonlighting and review biochemical and immunochemical evidence confirming that cyt c undergoes conformational changes during normal and altered cellular homeostasis.
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Center for Pediatrics and Adolescent Medicine, Medical Center, University of Freiburg , Mathildenstrasse 1, Freiburg D-79106, Germany.
authors.forename: Luciana
authors.initials: L
authors.lastname: Hannibal
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.
authors.forename: Florencia
authors.initials: F
authors.lastname: Tomasina
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
authors.forename: Daiana A
authors.initials: DA
authors.lastname: Capdevila
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.
authors.forename: Verónica
authors.initials: V
authors.lastname: Demicheli
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.
authors.forename: Verónica
authors.initials: V
authors.lastname: Tórtora
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
authors.forename: Damián
authors.initials: D
authors.lastname: Alvarez-Paggi
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota , MMC 196, 420 Delaware Street, Southeast, Minneapolis, Minnesota 55455, United States.
authors.forename: Ronald
authors.initials: R
authors.lastname: Jemmerson
authors.affiliation: Departamento de Química Inorgánica, Analítica y Química Física/INQUIMAE, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires , Pabellón 2, Ciudad Universitaria, C1428EHA Buenos Aires, Argentina.
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Murgida
authors.affiliation: Departamento de Bioquímica, Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.|Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República , Avda. General Flores 2125, 11800 Montevideo, Uruguay.
authors.forename: Rafael
authors.initials: R
authors.lastname: Radi
mesh_terms: D000818:Animals; D002308:Cardiolipins / Q000737:chemistry; D045304:Cytochromes c / Q000737:chemistry* / Q000378:metabolism*; D004560:Electricity; D005656:Fungal Proteins / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D010743:Phospholipids / Q000737:chemistry; D010940:Plant Proteins / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D017510:Protein Folding; D011499:Protein Processing, Post-Translational; D021381:Protein Transport
chemical_list: D002308:Cardiolipins; D005656:Fungal Proteins; D010743:Phospholipids; D010940:Plant Proteins; D045304:Cytochromes c