Assembly factors monitor sequential hemylation of cytochrome b to regulate mitochondrial translation.
Mitochondrial respiratory chain complexes convert chemical energy into a membrane potential by connecting electron transport with charge separation. Electron transport relies on redox cofactors that occupy strategic positions in the complexes. How these redox cofactors are assembled into the complexes is not known. Cytochrome b, a central catalytic subunit of complex III, contains two heme bs. Here, we unravel the sequence of events in the mitochondrial inner membrane by which cytochrome b is hemylated. Heme incorporation occurs in a strict sequential process that involves interactions of the newly synthesized cytochrome b with assembly factors and structural complex III subunits. These interactions are functionally connected to cofactor acquisition that triggers the progression of cytochrome b through successive assembly intermediates. Failure to hemylate cytochrome b sequesters the Cbp3-Cbp6 complex in early assembly intermediates, thereby causing a reduction in cytochrome b synthesis via a feedback loop that senses hemylation of cytochrome b.
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.
Markus
M
Hildenbeutel
Department of Biochemistry & Molecular Biology, Michigan State University, East Lansing, MI 48824.
Eric L
EL
Hegg
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.
Katharina
K
Stephan
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden.
Steffi
S
Gruschke
Centre de Génétique Moléculaire du Centre National de la Recherche Scientifique (CNRS), 91198 Gif-sur-Yvette, France.
Brigitte
B
Meunier
Department of Biochemistry and Biophysics, Center for Biomembrane Research, Stockholm University, SE-106 91 Stockholm, Sweden martin.ott@dbb.su.se.
Martin
M
Ott
D045303:Cytochromes b / Q000235:genetics / Q000378:metabolism*; D019143:Evolution, Molecular; D025461:Feedback, Physiological / Q000502:physiology; D050259:Genes, Mitochondrial / Q000235:genetics; D006418:Heme / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D010084:Oxidation-Reduction; D014176:Protein Biosynthesis / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
C435647:CBP3 protein, S cerevisiae; C088917:CBP4 protein, S cerevisiae; C561113:Cbp6 protein, S cerevisiae; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D029701:Saccharomyces cerevisiae Proteins; D006418:Heme; D045303:Cytochromes b