Mitochondria as cell targets of AZT (zidovudine).
1. The subject of this review is the interaction between AZT (zidovudine) and mitochondria as described in papers dealing with AZT therapy both in AIDS patients and in model systems--that is, in cultured cells and in isolated mitochondria. 2. The structure and function of mitochondria are briefly described with discussion of the theoretical frame for a detailed bioenergetic investigation. 3. Experimental work is reported showing that mitochondria are cell AZT targets: changes in the structure and function induced by long-term AZT therapy as investigated both in AIDS patients and in model systems. 4. The AZT inhibition of energy-supplying reactions is considered in detail in studies dealing with long-term treatment and studies in which AZT was added to isolated mitochondria. In particular, adenylate kinase, ADP/ATP translocase and DNA polymerase gamma are reported as molecular targets of AZT. 5. Some perspectives of AZT therapy from the study of the effect of AZT on mitochondrion biochemistry are briefly reported.
Barile
M
M
Dipartimento di Biochimica e Biologia Molecolare, Università degli Studi di Bari, and Centro di Studio sui Mitocondri e Metabolismo Energitico C.N.R., Italy. m.barile@biologia.uniba.it
Valenti
D
D
Quagliariello
E
E
Passarella
S
S
D000163:Acquired Immunodeficiency Syndrome / Q000188:drug therapy*; D000818:Animals; D002478:Cells, Cultured; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000187:drug effects; D004259:DNA-Directed DNA Polymerase / Q000187:drug effects; D054306:Dideoxynucleotides; D006801:Humans; D066298:In Vitro Techniques; D008928:Mitochondria / Q000187:drug effects* / Q000502:physiology / Q000648:ultrastructure; D013942:Thymine Nucleotides / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology*
D004272:DNA, Mitochondrial; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; D015215:Zidovudine; C052873:zidovudine triphosphate; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase