Impaired mitochondria-initiated crosstalk with lysosomes reciprocally aggravates mitochondrial defect through LManVI

Shengnan Li, Zhaoliang Shan, Guochun Zhao, Yuwei Li, Minghui Du, Xiuxiu Ti, Yuxue Gao, Wenting Li, Hui Zuo, Yan Wang () and Qing Zhang ()
Additional contact information
Shengnan Li: Nanjing University
Zhaoliang Shan: Nanjing University
Guochun Zhao: Nanjing University
Yuwei Li: Chinese Academy of Medical Sciences
Minghui Du: Chinese Academy of Medical Sciences
Xiuxiu Ti: Nanjing University
Yuxue Gao: Nanjing University
Wenting Li: Nanjing University
Hui Zuo: Nanjing University
Yan Wang: Chinese Academy of Medical Sciences
Qing Zhang: Nanjing University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: 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.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62147-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62147-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62147-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().