Biogenesis and dynamics of mitochondria during the cell cycle: significance of 3'UTRs.
Nowadays, we are facing a renaissance of mitochondria in cancer biology. However, our knowledge of the basic cell biology and on the timing and mechanisms that control the biosynthesis of mitochondrial constituents during progression through the cell cycle of mammalian cells remain largely unknown. Herein, we document the in vivo changes on mitochondrial morphology and dynamics that accompany cellular mitosis, and illustrate the following key points of the biogenesis of mitochondria during progression of liver cells through the cycle: (i) the replication of nuclear and mitochondrial genomes is synchronized during cellular proliferation, (ii) the accretion of OXPHOS proteins is asynchronously regulated during proliferation being the synthesis of beta-F1-ATPase and Hsp60 carried out also at G2/M and, (iii) the biosynthesis of cardiolipin is achieved during the S phase, although full development of the mitochondrial membrane potential (DeltaPsim) is attained at G2/M. Furthermore, we demonstrate using reporter constructs that the mechanism regulating the accretion of beta-F1-ATPase during cellular proliferation is controlled at the level of mRNA translation by the 3'UTR of the transcript. The 3'UTR-driven synthesis of the protein at G2/M is essential for conferring to the daughter cells the original phenotype of the parental cell. Our findings suggest that alterations on this process may promote deregulated beta-F1-ATPase expression in human cancer.
Martínez-Diez
Marta
M
Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Madrid, Spain.
Santamaría
Gema
G
Ortega
Alvaro D
AD
Cuezva
José M
JM
D020413:3' Untranslated Regions; D000818:Animals; D002453:Cell Cycle / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D002999:Clone Cells; D006224:Cricetinae; D022781:Hepatocytes / Q000166:cytology / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000235:genetics* / Q000378:metabolism* / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D020413:3' Untranslated Regions; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D025261:Mitochondrial Proton-Translocating ATPases