title: ES1 is a mitochondrial enlarging factor contributing to form mega-mitochondria in zebrafish cones.
abstract: Total mass of mitochondria increases during cell proliferation and differentiation through mitochondrial biogenesis, which includes mitochondrial proliferation and growth. During the mitochondrial growth, individual mitochondria have been considered to be enlarged independently of mitochondrial fusion. However, molecular basis for this enlarging process has been poorly understood. Cone photoreceptor cells in the retina possess large mitochondria, so-called mega-mitochondria that have been considered to arise via the enlarging process. Here we show that ES1 is a novel mitochondria-enlarging factor contributing to form mega-mitochondria in cones. ES1 is specifically expressed in cones and localized to mitochondria including mega-mitochondria. Knockdown of ES1 markedly reduced the mitochondrial size in cones. In contrast, ectopic expression of ES1 in rods significantly increased both the size of individual mitochondria and the total mass of the mitochondrial cluster without changing the number of them. RNA-seq analysis showed that ERRα and its downstream mitochondrial genes were significantly up-regulated in the ES1-expressing rods, suggesting facilitation of mitochondrial enlargement via ERRα-dependent processes. Furthermore, higher energy state was detected in the ES1-expressing rods, indicating that the enlarged mitochondria by ES1 are capable of producing high energy. ES1 is the mitochondrial protein that is first found to promote enlargement of individual mitochondria.
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Masuda
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Biological Sciences, Graduate School of Science, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Wada
authors.affiliation: Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan.|Department of Biological Sciences, Graduate School of Science, Osaka University, Suita, Osaka 565-0871, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Kawamura
mesh_terms: D000818:Animals; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D060172:Morpholinos / Q000235:genetics; D011960:Receptors, Estrogen; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D015027:Zebrafish / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D005136:Eye Proteins; D024101:Mitochondrial Proteins; D060172:Morpholinos; D011960:Receptors, Estrogen; D029961:Zebrafish Proteins; D000097983:ERRalpha Estrogen-Related Receptor; C107626:ES1 protein, zebrafish