title: Mitochondrial DNA depletion and respiratory chain enzyme deficiencies are present in peripheral blood mononuclear cells of HIV-infected patients with HAART-related lipodystrophy.
abstract: The main objective of the present study was to ascertain if mitochondrial DNA (mtDNA) depletion as reported in HIV-infected patients with highly active antiretroviral therapy (HAART)-related lipodystrophy (LD) implies any degree of mitochondrial respiratory chain (MRC) dysfunction. For this purpose, we evaluated HIV patients on different HAART schedules with LD (group A; n=12) and on HAART but without LD (group B; n=12), and untreated HIV-infected patients as controls (group C; n=24). mtDNA content was determined on peripheral blood mononuclear cells (PBMCs) with a real-time PCR method. Complex II, III and IV activities of the MRC were simultaneously measured spectrophotometrically, as were spontaneous and stimulated oxygen consumption by PBMCs. Compared to controls (group C, 100%), patients with LD (group A) showed a decreased mtDNA content (54%, P<0.001), which was associated with a decline in complex III (62%, P<0.05) and IV activity (69%, P<0.05) (both complexes partially encoded by mtDNA), but not in complex II activity (exclusively encoded by nuclear DNA). Patients in group B showed a similar pattern of mitochondrial dysfunction but to a lesser extent and without statistical significance. Respiratory activities in both treated groups (A and B) did not differ in comparison with controls. We conclude that mtDNA depletion occurring during HAART is associated with deficiencies in MRC complexes partially encoded by mtDNA, which are detectable by PBMCs. Presented in 'Late Breakers and Hot Topics' session at 6th International Congress on Drug Therapy in HIV Infection, Glasgow, UK, 17-21 November 2002.
authors.affiliation: Mitochondrial Research Lab, Muscle Research Unit, Dept. of Internal Medicine, (IDIBAPS), School of Medicine, Univ. of Barcelona, Spain. omiro@clinic.ub.es
authors.forename: Oscar
authors.initials: O
authors.lastname: Miró
authors.forename: Sònia
authors.initials: S
authors.lastname: López
authors.forename: Enric
authors.initials: E
authors.lastname: Pedrol
authors.forename: Benjamín
authors.initials: B
authors.lastname: Rodríguez-Santiago
authors.forename: Esteban
authors.initials: E
authors.lastname: Martínez
authors.forename: Anna
authors.initials: A
authors.lastname: Soler
authors.forename: Ana
authors.initials: A
authors.lastname: Milinkovic
authors.forename: Jordi
authors.initials: J
authors.lastname: Casademont
authors.forename: Virginia
authors.initials: V
authors.lastname: Nunes
authors.forename: Josep M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Francesc
authors.initials: F
authors.lastname: Cardellach
mesh_terms: D000328:Adult; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D004272:DNA, Mitochondrial / Q000378:metabolism*; D045222:Electron Transport Chain Complex Proteins; D005260:Female; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000473:pathology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000201:enzymology / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology*; D028361:Mitochondrial Diseases; D010101:Oxygen Consumption
chemical_list: D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins