| RRC ID |
76005
|
| Author |
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.
|
| Title |
A pair of transporters controls mitochondrial Zn2+ levels to maintain mitochondrial homeostasis.
|
| Journal |
Protein Cell
|
| 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.
|
| Volume |
13(3)
|
| Pages |
180-202
|
| Published |
2022-3-1
|
| DOI |
10.1007/s13238-021-00881-4
|
| PII |
10.1007/s13238-021-00881-4
|
| PMID |
34687432
|
| PMC |
PMC8901913
|
| MeSH |
Animals
Caenorhabditis elegans / genetics
Caenorhabditis elegans / metabolism
Cation Transport Proteins* / genetics
Homeostasis
Mitochondria* / metabolism
Zinc / metabolism
|
| Resource |
| C.elegans |
tm1108 |
