An integrase of endogenous retrovirus is involved in maternal mitochondrial DNA inheritance of the mouse

• Published in: Biochemical and biophysical research communications Vol. 366; no. 1; pp. 206 - 211
• Main Authors: Hayashida, Kenji, Omagari, Katsuhisa, Masuda, Jun-ichi, Kohno, Shigeru
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2008
• Subjects: Animals; DNA, Mitochondrial - metabolism; Endogenous retrovirus; Endogenous Retroviruses - genetics; Endonuclease; Eri15; Female; Integrase; Integrases - genetics; Maternal mitochondrial DNA inheritance; Mice - genetics; Mice, Inbred C57BL; Mothers; Ovary - physiology; Ovary - virology; Spag1; Sperm mitochondrial DNA deletion; tpis; Translocator of mitochondrial outer membrane; tpis; Integrase; Maternal mitochondrial DNA inheritance; Eri15; Endogenous retrovirus; Translocator of mitochondrial outer membrane; Spag1; Endonuclease; Sperm mitochondrial DNA deletion
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2007.11.127

The mechanism of maternal mitochondrial DNA (mtDNA) inheritance in animals can be said to be the selective elimination of sperm mtDNA via the elimination factor of the egg and a sperm mitochondria-specific factor. In 2005, we clarified that t-tpis (Spag1 isoform 1) is a mitochondria-specific translocator and the sperm factor, and furthermore estimated that the elimination factors of the egg are the divalent cation-dependent endonuclease and s-tpis (Spag1 isoform 2 and isoform 3) as the elimination system-specific chaperone [K. Hayashida, K. Omagari, J. Masuda, H. Hazama, Y. Kadokawa, K. Ohba, S. Kohno, The sperm mitochondria-specific translocator has a key role in maternal mitochondrial inheritance, Cell Biol. Int. 29 (2005) 472–481]. This time, using a recombinant Spag1 isoform 1 protein, a pull-down assay of ovary cytosol was performed and the elimination factors searched for. Surprisingly, an endogenous retroviral integrase fragment (Eri15) was identified using mass spectrometry of the electrophoresis band of the pull-down protein. Eri15 was detected as a complex of ∼500kDa with Spag1 isoform 2 or isoform 3 in native PAGE of the ovary cytosol. This strongly suggested that Eri15 is selectively transported into the sperm mitochondria matrix by Spag1 isoform 2 and 3 via Spag1 isoform 1 and that sperm mtDNA is destroyed, thus causing the establishment of maternal mtDNA inheritance.