Article available at http://dx.doi.org/10.1371/journal.pone.0000107
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 b-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 (DYm) is attained at G2/M. Furthermore, we
demonstrate using reporter constructs that the mechanism regulating the accretion of b-F1-ATPase during cellular
proliferation is controlled at the level of mRNA translation by the 39UTR of the transcript. The 39UTR-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 b-F1-ATPase expression in human cancer.
M.M-D, G.S. and A.D.O are/were recipients of predoctoral fellowships
from the Ministerio de Educación y Ciencia, Spain. This work was supported by
grants from the Ministerio de Sanidad (PI041255), Educación y Ciencia (SAF-2005-
4001 and BMC2001-0710)and Fundación Mutua Madrileña, Spain. The CBMSO is
the recipient of an institutional grant from Fundación Ramón Areces.
Peer reviewed