Mitochondrial calcium uniporter is essential for hearing and hair cell preservation in congenic FVB/NJ mice
In: Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-14
Online
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Zugriff:
Mitochondrial Ca2+ 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 Ca2+ channels result in a large influx of Ca2+. The intracellular rise in Ca2+ is partly balanced by the mitochondria which rapidly uptakes Ca2+ via a highly selective channel comprised of the main pore-forming subunit, the mitochondrial Ca2+ uniporter (MCU), and associated regulatory proteins. MCU thus contributes to Ca2+ buffering, ensuring cytosolic homeostasis, and is posited to have a critical role in hair cell function and hearing. To test this hypothesis, Ca2+ 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 Cdh23ahl allele to the FVB/NJ strain, due to the close proximity of these genes. Neither Mcu+/− nor Mcu−/− genotypes affected cochlear development, morphology, or Ca2+ 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 Ca2+ 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.
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Mitochondrial calcium uniporter is essential for hearing and hair cell preservation in congenic FVB/NJ mice
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Autor/in / Beteiligte Person: | Manikandan, Mayakannan ; Stepanyan, Ruben ; Perea, Elizabeth ; Deshmukh, Aditi R. ; Walker, Steven N. ; Alagramam, Kumar N. ; Wang, Danqi |
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Zeitschrift: | Scientific Reports, Jg. 11 (2021), Heft 1, S. 1-14 |
Veröffentlichung: | Nature Portfolio, 2021 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
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