| RRC ID |
85582
|
| 著者 |
Li S, Shan Z, Zhao G, Li Y, Du M, Ti X, Gao Y, Li W, Zuo H, Wang Y, Zhang Q.
|
| タイトル |
Impaired mitochondria-initiated crosstalk with lysosomes reciprocally aggravates mitochondrial defect through LManVI.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Mitochondria coordinate with lysosomes to maintain cellular homeomstasis. However, in mitochondrial defect condition, how they communicate is less clear. Here, utilizing dMterf4 RNAi fly model, we find that expression of lysosomal alpha-mannosidase VI (LManVI) is significantly downregulated. Mechanistically, we show that dMterf4 RNAi-triggered mitochondrial defect mediates downregulation of lysosomal LManVI through Med8/Tfb4-E(z)/pho axis, causing impairment of lysosomal function. Reciprocally, downregulation of lysosomal LManVI further decreases many mitochondrial genes expression through downregulation of transcriptional coactivator PGC-1, leading to aggravating the dMterf4 RNAi-mediated mitochondrial defect, suggesting that mitochondrial defect can crosstalk with lysosomes to make mitochondrial status worse in a positive feedback way. Finally, we demarcate that this interaction between mitochondria and lysosomes may be conserved in mammalian cells. Therefore, our findings unveil a communication mechanism between mitochondria and lysosomes in mitochondrial defect case, which provides insights about the treatments of related mitochondrial and lysosomal diseases through modulation of the mitochondria-lysosomes axis.
|
| 巻・号 |
16(1)
|
| ページ |
7304
|
| 公開日 |
2025-8-7
|
| DOI |
10.1038/s41467-025-62147-5
|
| PII |
10.1038/s41467-025-62147-5
|
| PMID |
40774949
|
| PMC |
PMC12332152
|
| MeSH |
Animals
Down-Regulation
Drosophila Proteins* / genetics
Drosophila Proteins* / metabolism
Drosophila melanogaster / genetics
Drosophila melanogaster / metabolism
Humans
Lysosomes* / metabolism
Mitochondria* / genetics
Mitochondria* / metabolism
RNA Interference
Transcription Factors / genetics
Transcription Factors / metabolism
|
| IF |
12.121
|
| リソース情報 |
| ショウジョウバエ |
15390R-2
14941R-2
4236R-1
3114R-2
9809R-1 |
