Short communication: reversible mitochondrial respiratory chain impairment during symptomatic hyperlactatemia associated with antiretroviral therapy.
Direct evidence confirming the hypothesis that a dysfunction of the mitochondrial respiratory chain (MRC) underlies the pathogenesis of hyperlactatemia associated with highly active antiretroviral therapy (HAART) is scarce. We studied mitochondrial DNA (mtDNA) content and MRC function in the skeletal muscle of an HIV-infected patient during an episode of symptomatic hyperlactatemia. Skeletal muscle biopsy was performed during the episode when the patient was symptomatic and 3 months later when the patient was clinically recovered. Assessment of mitochondria was performed using histological, polarographic, spectrophotometrical, and Southern blot and real time PCR DNA quantification methods. The histological study disclosed extensive mitochondrial impairment in the form of ragged-red fibers or equivalents on oxidative reactions. These findings were associated with an increase in mitochondrial content and a decrease in both mitochondrial respiratory capacity and MRC enzyme activities. Mitochondrial DNA content declined to 53% of control values. Mitochondrial abnormalities had almost disappeared later when the patient became asymptomatic. Our findings support the hypothesis that MRC dysfunction stands at the basis of HAART-related hyperlactatemia.
Miró
Oscar
O
Mitochondrial Research Laboratory, Department of Internal Medicine, Hospital Clínic, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), School of Medicine, University of Barcelona, Barcelona, Catalonia, Spain. omiro@clinic.ub.es
López
Sònia
S
Martínez
Esteban
E
Rodríguez-Santiago
Benjamín
B
Blanco
José L
JL
Milinkovic
Ana
A
Miró
Jose M
JM
Nunes
Virginia
V
Casademont
Jordi
J
Gatell
Josep M
JM
Cardellach
Francesc
F
D000140:Acidosis, Lactic / Q000209:etiology*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects*; D001706:Biopsy; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D004579:Electron Transport / Q000502:physiology*; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000201:enzymology / Q000473:pathology*; D018482:Muscle, Skeletal / Q000473:pathology
D004272:DNA, Mitochondrial