Mitochondrial DNA depletion and respiratory chain enzyme deficiencies are present in peripheral blood mononuclear cells of HIV-infected patients with HAART-related lipodystrophy.
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.
Miró
Oscar
O
Mitochondrial Research Lab, Muscle Research Unit, Dept. of Internal Medicine, (IDIBAPS), School of Medicine, Univ. of Barcelona, Spain. omiro@clinic.ub.es
López
Sònia
S
Pedrol
Enric
E
Rodríguez-Santiago
Benjamín
B
Martínez
Esteban
E
Soler
Anna
A
Milinkovic
Ana
A
Casademont
Jordi
J
Nunes
Virginia
V
Gatell
Josep M
JM
Cardellach
Francesc
F
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
D004272:DNA, Mitochondrial; D045222:Electron Transport Chain Complex Proteins