Zn^(2+)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 Zn^(2+)level is achieved to ma...Zn^(2+)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 Zn^(2+)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 Zn^(2+).We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn^(2+)exporter.Loss of SLC-30A9 leads to mitochondrial Zn^(2+)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 Zn^(2+)import.Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn^(2+)accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9.Moreover,we reveal that the endoplasmic reticulum contains the Zn^(2+)pool from which mitochondrial Zn^(2+)is imported.These findings establish the molecular basis for controlling the correct mitochondrial levels for normal mitochondrial structure and functions.展开更多
基金This work was supported by grants from the National Science Foundation of China(91954204 and 31730053)the National Basic Research Program of China(2017YFA0503403)Yunnan Province Science and Technology Department(#202001BB050077 and#202105AB160003).
文摘Zn^(2+)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 Zn^(2+)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 Zn^(2+).We demonstrate that SLC-30A9/ZnT9 is a mitochondrial Zn^(2+)exporter.Loss of SLC-30A9 leads to mitochondrial Zn^(2+)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 Zn^(2+)import.Loss of SLC-25A25 suppresses the abnormal mitochondrial Zn^(2+)accumulation and defective mitochondrial structure and functions caused by loss of SLC-30A9.Moreover,we reveal that the endoplasmic reticulum contains the Zn^(2+)pool from which mitochondrial Zn^(2+)is imported.These findings establish the molecular basis for controlling the correct mitochondrial levels for normal mitochondrial structure and functions.
