Mitochondrial biogenesis and mitochondrial activity during the progression of the cell cycle of human leukemic cells.
Mitochondrial (mt) biogenesis and mt function were investigated during the cell cycle of leukemic cells. The study shows that the activity of enzymes involved in oxidative phosphorylation increases in the early G1 phase. This increase in activity precedes that of other mt enzymes such as citrate synthase and adenylate kinase. Therefore, the synthesis of mt enzymes, needed for the reduplication of the mt mass in the course of the cell cycle, occurs in a sequential order. The enzymes of the system for oxidative phosphorylation are composed of several subunits. Some of these subunits are encoded on mtDNA and synthesized by mt-specific RNA and protein synthesis. This explains why inhibition of mt protein synthesis during the progression of the cell cycle of G1-enriched cells results in an increasing shortage of ATP. This lack of ATP results first in progression delay and, subsequently, in a cell cycle block in early G1. Furthermore, shortage of ATP impairs the increase in activity of at least one mt matrix enzyme. This study offers new information about a number of aspects of mt biogenesis and mt function during cell cycle progression and elucidates the cytostatic mechanism resulting from prolonged inhibition of mt protein synthesis.
Van den Bogert
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C
Laboratory of Physiological Chemistry, Medical School, State University, Groningen, The Netherlands.
Muus
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P
Haanen
C
C
Pennings
A
A
Melis
T E
TE
Kroon
A M
AM
D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D002453:Cell Cycle; D004318:Doxycycline / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000201:enzymology / Q000502:physiology*; D014176:Protein Biosynthesis; D014407:Tumor Cells, Cultured
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D004318:Doxycycline