Alternative Conformations of Cytochrome c: Structure, Function, and Detection

• Published in: Biochemistry (Easton) 2016-01, Vol.55 (3), p.407-428
• Main Authors: Hannibal, Luciana, Tomasina, Florencia, Capdevila, Daiana A, Demicheli, Verónica, Tórtora, Verónica, Alvarez-Paggi, Damián, Jemmerson, Ronald, Murgida, Daniel H, Radi, Rafael
• Format: Article
• Language: English
• Subjects: Animals; Cardiolipins - chemistry; Cytochromes c - chemistry; Cytochromes c - metabolism; Electricity; Fungal Proteins - chemistry; Fungal Proteins - metabolism; Humans; Intracellular Space - metabolism; Phospholipids - chemistry; Plant Proteins - chemistry; Plant Proteins - metabolism; Protein Conformation; Protein Folding; Protein Processing, Post-Translational; Protein Transport
• ISSN: 0006-2960; 1520-4995
• DOI: 10.1021/acs.biochem.5b01385

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.