T-cell-restricted intracellular antigen 1 facilitates mitochondrial fragmentation by enhancing the expression of mitochondrial fission factor.
Mitochondrial morphology is dynamically regulated by the formation of small fragmented units or interconnected mitochondrial networks, and this dynamic morphological change is a pivotal process in normal mitochondrial function. In the present study, we identified a novel regulator responsible for the regulation of mitochondrial dynamics. An assay using CHANG liver cells stably expressing mitochondrial-targeted yellow fluorescent protein (mtYFP) and a group of siRNAs revealed that T-cell intracellular antigen protein-1 (TIA-1) affects mitochondrial morphology by enhancing mitochondrial fission. The function of TIA-1 in mitochondrial dynamics was investigated through various biological approaches and expression analysis in human specimen. Downregulation of TIA-1-enhanced mitochondrial elongation, whereas ectopic expression of TIA-1 resulted in mitochondria fragmentation. In addition, TIA-1 increased mitochondrial activity, including the rate of ATP synthesis and oxygen consumption. Further, we identified mitochondrial fission factor (MFF) as a direct target of TIA-1, and showed that TIA-1 promotes mitochondrial fragmentation by enhancing MFF translation. TIA-1 null cells had a decreased level of MFF and less mitochondrial Drp1, a critical factor for mitochondrial fragmentation, thereby enhancing mitochondrial elongation. Taken together, our results indicate that TIA-1 is a novel factor that facilitates mitochondrial dynamics by enhancing MFF expression and contributes to mitochondrial dysfunction.
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Hyosun
H
Tak
Department of Pathology, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Jung Woo
JW
Eun
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Jihye
J
Kim
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
So Jung
SJ
Park
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Chongtae
C
Kim
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Eunbyul
E
Ji
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Heejin
H
Lee
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Hoin
H
Kang
Department of East-West Medical Science, Graduate School of East-West Medical Science, Kyung Hee University, Yongin, South Korea.
Dong-Hyung
DH
Cho
Department of Pathology, Seoul National University College of Medicine, Seoul, South Korea.
Kyungbun
K
Lee
Department of Molecular Science and Technology, Ajou University, Suwon, South Korea.
Wook
W
Kim
Department of Pathology, The Catholic University of Korea College of Medicine, Seoul, South Korea.|Cancer Evolution Research Center, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Suk Woo
SW
Nam
Department of Biochemistry, The Catholic University of Korea College of Medicine, Seoul, South Korea.|Cancer Evolution Research Center, The Catholic University of Korea College of Medicine, Seoul, South Korea.|Institute for Aging and Metabolic Disease, The Catholic University of Korea College of Medicine, Seoul, South Korea.
Eun Kyung
EK
Lee
D020413:3' Untranslated Regions; D000255:Adenosine Triphosphate / Q000096:biosynthesis; D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D034281:Dynamins; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D035683:MicroRNAs / Q000378:metabolism; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010101:Oxygen Consumption; D010957:Plasmids / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D000074019:T-Cell Intracellular Antigen-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*
D020413:3' Untranslated Regions; D001426:Bacterial Proteins; D008164:Luminescent Proteins; D008565:Membrane Proteins; C533267:Mff protein, human; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000074019:T-Cell Intracellular Antigen-1; C054562:yellow fluorescent protein, Bacteria; D000255:Adenosine Triphosphate; D020558:GTP Phosphohydrolases; C110768:DNM1L protein, human; D034281:Dynamins