Mitochondrial oxidative phosphorylation protein levels in peripheral blood mononuclear cells correlate with levels in subcutaneous adipose tissue within samples differing by HIV and lipoatrophy status.
Depletion of mitochondrial DNA (mtDNA) and mtDNA-encoded respiratory chain proteins in subcutaneous (SC) fat from patients with HIV lipoatrophy have clearly demonstrated the role of mitochondrial dysfunction in this syndrome. Research in HIV lipoatrophy, however, has been severely hampered by the lack of a suitable surrogate marker in blood or other easily obtained clinical specimens as fat biopsies are invasive and mtDNA levels in peripheral blood mononuclear cells (PBMC) do not consistently correlate with the disease process. We used a simple, rapid, quantitative 2-site dipstick immunoassay to measure OXPHOS enzymes Complex I (CI) and Complex IV (CIV), and rtPCR to measure mtDNA in 26 matched SC fat and PBMC specimens previously banked from individuals on potent antiretroviral (ARV) therapy with HIV lipoatrophy, on similar ARV therapy without lipoatrophy, and in HIV seronegative controls. Significant correlations were found between the respective PBMC and fat levels for both CI (r = 0.442, p = 0.024) and for CIV (r = 0.507, p = 0.008). Both CI and CIV protein levels were also significantly reduced in both PBMCs and fat in lipoatrophic subjects compared to HIV seronegative controls (p < or = 0.05), while a comparative reduction in mtDNA levels in lipoatrophic subjects was observed only in fat. We conclude that CI and CIV levels in PBMCs correlate to their respective levels in fat and may have utility as surrogate markers of mitochondrial dysfunction in lipoatrophy.
Hawaii AIDS Clinical Research Program, John A. Burns School of Medicine, University of Hawaii-Manoa, Honolulu, Hawaii 96816, USA. shikuma@hawaii.edu
Cecilia M
CM
Shikuma
Mariana
M
Gerschenson
Dominic
D
Chow
Daniel E
DE
Libutti
John H
JH
Willis
James
J
Murray
Roderick A
RA
Capaldi
Michael
M
Marusich
D000328:Adult; D004272:DNA, Mitochondrial / Q000032:analysis; D005260:Female; D015658:HIV Infections / Q000150:complications* / Q000188:drug therapy; D039682:HIV-Associated Lipodystrophy Syndrome / Q000175:diagnosis*; D006801:Humans; D007118:Immunoassay / Q000379:methods; D007963:Leukocytes, Mononuclear / Q000737:chemistry*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000032:analysis*; D010085:Oxidative Phosphorylation; D016133:Polymerase Chain Reaction / Q000379:methods; D011506:Proteins / Q000378:metabolism*; D013223:Statistics as Topic; D050151:Subcutaneous Fat / Q000737:chemistry*
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D011506:Proteins