Distinctive biochemistry in the trypanosome mitochondrial intermembrane space suggests a model for stepwise evolution of the MIA pathway for import of cysteine-rich proteins.
Mia40-dependent disulphide bond exchange is used by animals, yeast, and probably plants for import of small, cysteine-rich proteins into the mitochondrial intermembrane space (IMS). During import, electrons are transferred from the imported substrate to Mia40 then, via the sulphydryl oxidase Erv1, into the respiratory chain. Curiously, however, there are protozoa which contain substrates for Mia40-dependent import, but lack Mia40. There are also organisms where Erv1 is present in the absence of respiratory chain components. In accommodating these and other relevant observations pertaining to mitochondrial cell biology, we hypothesise that the ancestral IMS import pathway for disulphide-bonded proteins required only Erv1 (but not Mia40) and identify parasites in which O(2) is the likely physiological oxidant for Erv1.
Allen
James W A
JW
Department of Biochemistry, University of Oxford, South Parks Road, Oxford, UK. james.allen@bioch.ox.ac.uk
Ferguson
Stuart J
SJ
Ginger
Michael L
ML
D000595:Amino Acid Sequence; D000693:Anaerobiosis; D000818:Animals; D003545:Cysteine / Q000378:metabolism; D003579:Cytochrome Reductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism*; D004220:Disulfides / Q000378:metabolism; D004579:Electron Transport; D019143:Evolution, Molecular; D033681:Mitochondrial Membrane Transport Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism; D010802:Phylogeny; D021381:Protein Transport; D015800:Protozoan Proteins / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D014345:Trypanosoma / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure
D004220:Disulfides; D033681:Mitochondrial Membrane Transport Proteins; D015800:Protozoan Proteins; D045304:Cytochromes c; D003579:Cytochrome Reductases; D003545:Cysteine; D010100:Oxygen