Small mitochondrial protein NERCLIN regulates cardiolipin homeostasis and mitochondrial ultrastructure
| Autor: | Pooja Manjunath, Jouni Kvist, Sundar Baral, Reijo Käkelä, Jayasimman Rajendran, Rubén Torregrosa-Muñumer, Henna Tyynismaa, Yang Yang, Svetlana Konovalova, Xiaonan Liu, Minna Holopainen, Pentti Somerharju, Markku Varjosalo |
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| Rok vydání: | 2021 |
| Předmět: |
Phosphatidylglycerol
0303 health sciences Phospholipid Matrix (biology) Cell biology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine chemistry Cardiolipin Prohibitin Inner mitochondrial membrane 030217 neurology & neurosurgery Function (biology) Homeostasis 030304 developmental biology |
| DOI: | 10.1101/2021.01.03.424667 |
| Popis: | Cardiolipin (CL) is an essential phospholipid for mitochondrial structure and function. Here we present a small mitochondrial protein, NERCLIN, as a negative regulator of CL homeostasis and mitochondrial ultrastructure. Primate-specific NERCLIN is expressed ubiquitously fromGRPEL2locus on a tightly regulated low level, but induced by heat stress. NERCLIN overexpression severely disrupts mitochondrial cristae structure and induces mitochondrial fragmentation. Proximity labeling suggested interactions of NERCLIN with CL synthesis and prohibitin complexes on the matrix side of the inner mitochondrial membrane. Lipid analysis indicated that NERCLIN regulates mitochondrial CL content. The regulation may occur directly through interaction with PTPMT1, a proximal partner on the CL synthesis pathway, as its product phosphatidylglycerol was also reduced by NERCLIN. We propose that NERCLIN contributes to stress-induced adaptation of mitochondrial dynamics and turnover by regulating the mitochondrial CL content. Our findings add NERCLIN to the group of recently identified small mitochondrial proteins with important regulatory functions. |
| Databáze: | OpenAIRE |
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