Gimap3 regulates tissue-specific mitochondrial DNA segregation.
Mitochondrial DNA (mtDNA) sequence variants segregate in mutation and tissue-specific manners, but the mechanisms remain unknown. The segregation pattern of pathogenic mtDNA mutations is a major determinant of the onset and severity of disease. Using a heteroplasmic mouse model, we demonstrate that Gimap3, an outer mitochondrial membrane GTPase, is a critical regulator of this process in leukocytes. Gimap3 is important for T cell development and survival, suggesting that leukocyte survival may be a key factor in the genetic regulation of mtDNA sequence variants and in modulating human mitochondrial diseases.
Research Program of Molecular Neurology and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Riikka
R
Jokinen
Paula
P
Marttinen
Helen Katarin
HK
Sandell
Tuula
T
Manninen
Heli
H
Teerenhovi
Timothy
T
Wai
Daniella
D
Teoli
J C
JC
Loredo-Osti
Eric A
EA
Shoubridge
Brendan J
BJ
Battersby
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006239:Haplotypes / Q000235:genetics*; D006413:Hematopoietic System / Q000378:metabolism; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007962:Leukocytes / Q000166:cytology / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013154:Spleen / Q000378:metabolism
D004272:DNA, Mitochondrial; C425002:Ian4 protein, mouse; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins