Regulation of mitochondrial morphology and cell survival by Mitogenin I and mitochondrial single-stranded DNA binding protein

• Published in: Biochimica et biophysica acta Vol. 1760; no. 9; pp. 1364 - 1372
• Main Authors: Arakaki, Naokatu, Nishihama, Takeshi, Kohda, Akira, Owaki, Hiroyuki, Kuramoto, Yoshinori, Abe, Reika, Kita, Toshiyuki, Suenaga, Midori, Himeda, Toshiki, Kuwajima, Masamichi, Shibata, Hirofumi, Higuti, Tomihiko
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2006
• Subjects: Amino Acid Sequence; Animals; Apoptosis; Cell Line; Cell Survival; DNA-Binding Proteins - chemistry; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fission/fusion; Gene Silencing; JVS; Mice; Mitochondria; Mitochondria - metabolism; Mitochondrial biogenesis; Mitochondrial Proteins - chemistry; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Molecular Sequence Data; mtSSB; Nuclear Proteins; PDIP38; PBS; RT; PDIP38; mito-DsRed1; JVS; FDD; EGFP; mtSSB; GFP; DMEM; Mitochondria; Mitochondrial biogenesis; PI; DASPEI; Fission/fusion; Apoptosis
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2006.05.012

We found that a mouse homolog of human DNA polymerase delta interacting protein 38, referred to as Mitogenin I in this paper, and mitochondrial single-stranded DNA-binding protein (mtSSB), identified as upregulated genes in the heart of mice with juvenile visceral steatosis, play a role in the regulation of mitochondrial morphology. We demonstrated that overexpression of Mitogenin I or mtSSB increased elongated or fragmented mitochondria in mouse C2C12 myoblast cells, respectively. On the other hand, the silencing of Mitogenin I or mtSSB by RNA interference led to an increase in fragmented or elongated mitochondria in the cells, respectively, suggesting that Mitogenin I and mtSSB are involved in the processes of mitochondrial fusion and fission, respectively. In addition, we showed that the silencing of Mitogenin I resulted in an increase in the number of trypan blue-positive cells and the silencing of mtSSB resulted in an enhancement of the sensitivity of the cells to apoptotic stimulation by etoposide. The present results demonstrated that these proteins play a role in cell survival.