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.
Jokinen
Riikka
R
Research Program of Molecular Neurology and Institute of Biomedicine, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland.
Marttinen
Paula
P
Sandell
Helen Katarin
HK
Manninen
Tuula
T
Teerenhovi
Heli
H
Wai
Timothy
T
Teoli
Daniella
D
Loredo-Osti
J C
JC
Shoubridge
Eric A
EA
Battersby
Brendan J
BJ
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