Mutation in keratin 18 induces mitochondrial fragmentation in liver-derived epithelial cells.
Microtubules (MTs) and microfilaments (MFs) are known to modulate mitochondrial morphology, distribution and function. However, little is known evidence about the role of intermediate filaments (IFs) in modulating mitochondria except desmin. To investigate whether or not the IFs regulate mitochondrial morphology, distribution, and function, we manipulated the IFs of cultured epithelial cells to express a mutant keratin 18 (K18). In contrast to the filamentous expression of wild K18, mutant K18 induced aggregation of K8/18, showing no fine IF network in the cells. In mutant K18-transfected cells, the mitochondria were fragmented into small spheroids, although they were observed as mitochondrial fibers in un-transfected or wild K18-transfected cells. Fluorescence recovery after photobleaching of fluorescence-labeled mitochondria was markedly less in the mutant K18-transfected cells, although a significant recovery was confirmed in wild K18-transfected cells. These findings suggest that the IFs are important for the maintenance of normal mitochondrial structures.
Kumemura
Hiroto
H
Division of Gastroenterology, Department of Medicine and Research Center for Innovative Cancer Therapy, Kurume University School of Medicine, 67 Asahi-Machi, Kurume 830-0011, Japan.
Harada
Masaru
M
Yanagimoto
Chikatoshi
C
Koga
Hironori
H
Kawaguchi
Takumi
T
Hanada
Shinichiro
S
Taniguchi
Eitaro
E
Ueno
Takato
T
Sata
Michio
M
D008841:Actin Cytoskeleton / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D053538:Keratin-18 / Q000235:genetics*; D008107:Liver Diseases / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D014162:Transfection
D005456:Fluorescent Dyes; D053538:Keratin-18