Contact sites from human placental mitochondria: characterization and role in progesterone synthesis.
To understand the functional compartmentalization of human placental mitochondria, we analyzed the composition and steroidogenic activity of contact sites. Several fractions containing contact sites were isolated using osmotic shock treatment and sucrose gradient centrifugation. These fractions contained various proteins and marker enzymes associated with mitochondrial membranes. The fractions containing the cytochrome P450 side chain cleavage system, cholesterol, nicotinamide adenine dinucleotide phosphate-isocitrate dehydrogenase, porin, and adenosine 5(')-triphosphate-diphosphohydrolase activity showed the capacity to synthesize progesterone. Our observations indicate that all necessary elements and enzymes for steroidogenesis are present and functional in placental mitochondrial contact sites. This organization may facilitate the metabolism of cholesterol delivered to the outer mitochondrial membrane into steroid hormones by the inner mitochondrial membrane cholesterol side chain cleavage system.
Uribe
Aida
A
Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Apdo. Postal 70-159, 04510 Mexico, DF, Mexico.
Strauss
Jerome F
JF
Martínez
Federico
F
D000263:Adenylate Kinase / Q000378:metabolism; D001081:Apyrase / Q000378:metabolism; D001665:Binding Sites; D015153:Blotting, Western; D002784:Cholesterol / Q000378:metabolism; D003580:Cytochromes / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008995:Monoamine Oxidase / Q000378:metabolism; D010920:Placenta / Q000201:enzymology / Q000378:metabolism*; D018272:Porins / Q000378:metabolism; D011374:Progesterone / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013347:Subcellular Fractions; D013385:Succinate Dehydrogenase / Q000378:metabolism; D013997:Time Factors
D003580:Cytochromes; D018272:Porins; D011374:Progesterone; D002784:Cholesterol; D007521:Isocitrate Dehydrogenase; D013385:Succinate Dehydrogenase; D008995:Monoamine Oxidase; D000263:Adenylate Kinase; D001081:Apyrase