Molecular and bioenergetic differences between cells with African versus European inherited mitochondrial DNA haplogroups: Implications for population susceptibility to diseases

M. Cristina Kenney, Marilyn Chwa, Shari R. Atilano, Payam Falatoonzadeh, Claudio Ramirez, Deepika Malik, Mohamed Tarek, Javier Cáceres del Carpio, Anthony B. Nesburn, David S. Boyer, Baruch D. Kuppermann, Marquis P. Vawter, S. Michal Jazwinski, Michael V. Miceli, Douglas C. Wallace, Nitin Udar

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

118 Citas (Scopus)

Resumen

The geographic origins of populations can be identified by their maternally inherited mitochondrial DNA (mtDNA) haplogroups. This study compared human cybrids (cytoplasmic hybrids), which are cell lines with identical nuclei but mitochondria from different individuals with mtDNA from either the H haplogroup or L haplogroup backgrounds. The most common European haplogroup is H while individuals of maternal African origin are of the L haplogroup. Despite lower mtDNA copy numbers, L cybrids had higher expression levels for nine mtDNA-encoded respiratory complex genes, decreased ATP (adenosine triphosphate) turnover rates and lower levels of reactive oxygen species production, parameters which are consistent with more efficient oxidative phosphorylation. Surprisingly, GeneChip arrays showed that the L and H cybrids had major differences in expression of genes of the canonical complement system (5 genes), dermatan/chondroitin sulfate biosynthesis (5 genes) and CCR3 (chemokine, CC motif, receptor 3) signaling (9 genes). Quantitative nuclear gene expression studies confirmed that L cybrids had (a) lower expression levels of complement pathway and innate immunity genes and (b) increased levels of inflammation-related signaling genes, which are critical in human diseases. Our data support the hypothesis that mtDNA haplogroups representing populations from different geographic origins may play a role in differential susceptibilities to diseases.

Idioma originalInglés
Páginas (desde-hasta)208-219
Número de páginas12
PublicaciónBiochimica et Biophysica Acta - Molecular Basis of Disease
Volumen1842
N.º2
DOI
EstadoPublicada - feb. 2014
Publicado de forma externa

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