A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Ma, T.; Zhao, L.; Zhang, J.; Tang, R.; Wang, X.; Liu, N.; Zhang, Q.; Wang, F.; Li, M.; Shan, Q.; Yang, Y.; Yin, Q.; Yang, L.; Gan, Q.; Yang, C.

doi:10.1101/2021.07.21.453180

bioRxiv · 10.1101/2021.07.21.453180

A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis

Ma, T.·Zhao, L.·Zhang, J.·Tang, R.·Wang, X.·Liu, N.·Zhang, Q.·Wang, F.·Li, M.·Shan, Q.·Yang, Y.·Yin, Q.·Yang, L.·Gan, Q.·Yang, C.

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Abstract

Zn2+ is required for the activity of many mitochondrial proteins, which regulate mitochondrial dynamics, apoptosis and mitophagy. However, it is not understood how the proper mitochondrial Zn2+ level is achieved to maintain mitochondrial homeostasis. Using Caenorhabditis elegans, we reveal here that a pair of mitochondrion-localized transporters controls the mitochondrial level of Zn2+. We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn2+ exporter. Loss of SLC-30A9 leads to mitochondrial Zn2+ accumulation, which damages mitochondria, impairs animal development and shortens the life span. We further identify SLC-25A25/SCaMC-2 as an important regulator of mitochondrial Zn2+ import. Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn2+ accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9. Moreover, we reveal that the endoplasmic reticulum contains the Zn2+ pool from which mitochondrial Zn2+ is imported. These findings establish the molecular basis for controlling the correct mitochondrial Zn2+ levels for normal mitochondrial structure and functions. SummaryZn2+ is a trace ion essential for the function of many mitochondrial proteins. It is not known how mitochondrial Zn2+ levels are regulated. Ma at al. identify transporters that mediate mitochondrial Zn2+ export and import to maintain mitochondrial homeostasis.

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Ma, T., Zhao, L., Zhang, J., Tang, R., Wang, X., Liu, N., Zhang, Q., Wang, F., Li, M., Shan, Q., Yang, Y., Yin, Q., Yang, L., Gan, Q., Yang, C.. 2021-07-21. A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis. https://doi.org/10.1101/2021.07.21.453180

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