| First Author | Manikandan M | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 9660 |
| PubMed ID | 33958614 | Mgi Jnum | J:316339 |
| Mgi Id | MGI:6713048 | Doi | 10.1038/s41598-021-88841-0 |
| Citation | Manikandan M, et al. (2021) Mitochondrial calcium uniporter is essential for hearing and hair cell preservation in congenic FVB/NJ mice. Sci Rep 11(1):9660 |
| abstractText | Mitochondrial Ca(2+) regulates a wide range of cell processes, including morphogenesis, metabolism, excitotoxicity, and survival. In cochlear hair cells, the activation of mechano-electrical transduction and voltage-gated Ca(2+) channels result in a large influx of Ca(2+). The intracellular rise in Ca(2+) is partly balanced by the mitochondria which rapidly uptakes Ca(2+) via a highly selective channel comprised of the main pore-forming subunit, the mitochondrial Ca(2+) uniporter (MCU), and associated regulatory proteins. MCU thus contributes to Ca(2+) buffering, ensuring cytosolic homeostasis, and is posited to have a critical role in hair cell function and hearing. To test this hypothesis, Ca(2+) homeostasis in hair cells and cochlear function were investigated in FVB/NJ mice carrying the knockout allele of Mcu (Mcu(+/-) or Mcu(-/-)). The Mcu knockout allele, which originated in C57BL/6 strain cosegregated along with Cdh23(ahl) allele to the FVB/NJ strain, due to the close proximity of these genes. Neither Mcu(+/-) nor Mcu(-/-) genotypes affected cochlear development, morphology, or Ca(2+) homeostasis of auditory hair cells in the first two postnatal weeks. However, Mcu(-/-) mice displayed high-frequency hearing impairment as early as 3 weeks postnatal, which then progressed to profound hearing loss at all frequencies in about 6 months. In Mcu(+/-) mice, significantly elevated ABR thresholds were observed at 6 months and 9 months of age only at 32 kHz frequency. In three-month-old Mcu(-/-) mice, up to 18% of the outer hair cells and occasionally some inner hair cells were missing in the mid-cochlear region. In conclusion, mitochondrial Ca(2+) uniporter is not required for the development of cochlea in mice, but is essential for hearing and hair cell preservation in congenic FVB/NJ mice. |
