Naslov
The human mitochondrial NME6 interacts with RCC1L and impacts respiration.

Autori
Proust, Bastien ; Radić, Martina ; Škrobot Vidaček, Nikolina ; Tokarska-Schlattner, Malgorzata ; Schlattner, Uwe ; Herak Bosnar, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology: From Science to Knowledge (HDBMB22)

Mjesto i datum
Brela, Hrvatska, 28.09.2022. - 01.10.2022

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
Mitochondria ; NME6 ; OXPHOS ; Respiratory chain

Sažetak
NME6 is a member of the nucleoside diphosphate kinase (NDPK/NME/Nm23) family, a group of proteins known to catalyze the transfer of gamma phosphate from NTPs to NDPs (NDPK activity). The ping-pong reaction involves the phosphorylation of a histidine residue within the catalytic site, strictly conserved among NME members. The family is divided in two groups based on the structure and phylogenetic analysis. The well-studied Group I members (NME1-4) are enzymatically active while the less-described Group II members (NME5-9) fail to display the NDPK activity. To date, only three NMEs are targeted to mitochondria: NME3 localizing at the mitochondrial outer membrane, NME4 localizing at the mitochondrial inner membrane, either facing inter-membrane space or matrix, and NME6. Mitochondria are the center of aerobic respiration, where Krebs cycle’s products, oxygen and ADP are used by the electron transport chain (ETC) to produce ATP. Mitochondria carry their own DNA and encode for 13 proteins, all constituent of the ETC complexes and indispensable for ETC function. We focused our efforts on studying the barely explored human NME6 protein. Using confocal microscopy and cell fractionation, we confirmed NME6 to be a mitochondrial, matrix facing protein. Co-immunoprecipitation experiments revealed an interaction between NME6 and RCC1L, another matrix facing protein involved in mitochondrial ribosome biogenesis and associated with de novo biosynthesis of mitochondria-encoded protein. Our oxygraphy analysis revealed a strong negative impact of NME6 overexpression on mitochondrial respiration. Accordingly, western blot analysis uncovered a downregulation of respiratory complex III protein UQCRC2 and the mitochondria-encoded complex IV protein COXII. Altogether, our research shed new light on the human NME6 protein, indicating its fundamental role in the regulation of mitochondrial respiration, independent of its enzymatic activity, and probably in concert with RCC1L. Our results provide solid basis for further investigation of the NME6 function within mitochondria.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

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