MIDAS/GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction.
To investigate the regulatory system in mitochondrial biogenesis involving crosstalk between the mitochondria and nucleus, we found a factor named MIDAS (mitochondrial DNA absence sensitive factor) whose expression was enhanced by the absence of mitochondrial DNA (mtDNA). In patients with mitochondrial diseases, MIDAS expression was increased only in dysfunctional muscle fibers. A majority of MIDAS localized to mitochondria with a small fraction in the Golgi apparatus in HeLa cells. To investigate the function of MIDAS, we stably transfected HeLa cells with an expression vector carrying MIDAS cDNA or siRNA. Cells expressing the MIDAS protein and the siRNA constitutively showed an increase and decrease in the total mass of mitochondria, respectively, accompanying the regulation of a mitochondria-specific phospholipid, cardiolipin. In contrast, amounts of the mitochondrial DNA, RNA and proteins did not depend upon MIDAS. Thus, MIDAS is involved in the regulation of mitochondrial lipids, leading to increases of total mitochondrial mass in response to mitochondrial dysfunction.
Nakashima-Kamimura
Naomi
N
Department of Biochemistry and Cell Biology, Institute of Development and Aging Sciences, Graduate School of Medicine, Nippon Medical School, 1-396 Kosugi-cho, Kawasaki, Kanagawa 211-8533, Japan.
Asoh
Sadamitsu
S
Ishibashi
Yoshitomo
Y
Mukai
Yuri
Y
Shidara
Yujiro
Y
Oda
Hideaki
H
Munakata
Kae
K
Goto
Yu-Ichi
Y
Ohta
Shigeo
S
D002308:Cardiolipins / Q000378:metabolism; D002467:Cell Nucleus / Q000235:genetics*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004272:DNA, Mitochondrial / Q000032:analysis / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008931:Mitochondria, Muscle / Q000378:metabolism* / Q000473:pathology* / Q000648:ultrastructure; D024101:Mitochondrial Proteins / Q000378:metabolism; D008933:Mitochondrial Swelling; D018485:Muscle Fibers, Skeletal / Q000378:metabolism / Q000473:pathology; D021381:Protein Transport; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism
D002308:Cardiolipins; D004272:DNA, Mitochondrial; C429024:GOLPH3 protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D000077278:RNA, Mitochondrial; D034741:RNA, Small Interfering; D012313:RNA