2. Academic Validation
  3. SLC-30A9 is required for Zn2+ homeostasis, Zn2+ mobilization, and mitochondrial health

SLC-30A9 is required for Zn2+ homeostasis, Zn2+ mobilization, and mitochondrial health

  • Proc Natl Acad Sci U S A. 2021 Aug 31;118(35):e2023909118. doi: 10.1073/pnas.2023909118.
Huichao Deng 1 2,  Xinhua Qiao 1,  Ting Xie 1 3,  Wenfeng Fu 1 2,  Hang Li 1 2,  Yanmei Zhao 4,  Miaomiao Guo 1 2,  Yaqian Feng 5,  Ligong Chen 5,  Yan Zhao 1,  Long Miao 2 4,  Chang Chen 6 2,  Kang Shen 7 8,  Xiangming Wang 6
Affiliations

Affiliations

  • 1 National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 2 College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
  • 3 School of Basic Medical Sciences, Southwest Medical University, Luzhou 646000, China.
  • 4 Key Laboratory of RNA Biology, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
  • 5 School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology (Ministry of Education), Tsinghua University, Beijing 100084, China.
  • 6 National Laboratory of Biomacromolecules, Chinese Academy of Sciences Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China; [email protected] [email protected] [email protected].
  • 7 HHMI, Stanford University, Stanford, CA 94305; [email protected] [email protected] [email protected].
  • 8 Department of Biology, Stanford University, Stanford, CA 94305.
PMID: 34433664 DOI: 10.1073/pnas.2023909118
Abstract

The trace element zinc is essential for many aspects of physiology. The mitochondrion is a major Zn2+ store, and excessive mitochondrial Zn2+ is linked to neurodegeneration. How mitochondria maintain their Zn2+ homeostasis is unknown. Here, we find that the SLC-30A9 transporter localizes on mitochondria and is required for export of Zn2+ from mitochondria in both Caenorhabditis elegans and human cells. Loss of slc-30a9 leads to elevated Zn2+ levels in mitochondria, a severely swollen mitochondrial matrix in many tissues, compromised mitochondrial metabolic function, reductive stress, and induction of the mitochondrial stress response. SLC-30A9 is also essential for organismal fertility and sperm activation in C. elegans, during which Zn2+ exits from mitochondria and acts as an activation signal. In slc-30a9-deficient neurons, misshapen mitochondria show reduced distribution in axons and dendrites, providing a potential mechanism for the Birk-Landau-Perez cerebrorenal syndrome where an SLC30A9 mutation was found.

Keywords

Birk–Landau–Perez cerebrorenal syndrome; SLC-30A9; Zn2+ transporters; mitochondria.

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