Polyphosphate and tyrosine phosphorylation in the N-terminal
domain of the human mitochondrial Lon protease disrupts its
functions

J 2024

Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions

KUNOVA, Nina; Gabriela ONDROVICOVA; Jacob A BAUER; Veronika KRAJCOVICOVA; Matyáš PINKAS et al.

Základní údaje

Originální název

Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions

Autoři

Vydání

Nature Scientific Reports, BERLIN, NATURE PORTFOLIO, 2024, 2045-2322

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30201 Cardiac and Cardiovascular systems

Stát vydavatele

Německo

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.900

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14740/24:00138972

Organizační jednotka

Středoevropský technologický institut

Klíčová slova anglicky

COMPUTED-TOMOGRAPHY; IMAGE-RECONSTRUCTION; CT

Štítky

CF CRYO, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 9. 6. 2025 15:38, Mgr. Eva Dubská

Anotace

V originále

Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.

Návaznosti

EF18_046/0015974, projekt VaV

Název: Modernizace České infrastruktury pro integrativní strukturní biologii

90242, velká výzkumná infrastruktura

Název: CIISB III

Citovat

KUNOVA, Nina; Gabriela ONDROVICOVA; Jacob A BAUER; Veronika KRAJCOVICOVA; Matyáš PINKAS; Barbora STOJKOVICOVA; Henrieta HAVALOVA; Veronika LUKACOVA; Lenka KOHUTOVA; Julius KOSTAN; Lucia MARTINAKOVA; Peter BARATH; Jiří NOVÁČEK; Sebastian ZOLL; Sami KEREICHE; Eva KUTEJOVA a Vladimir PEVALA. Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions. Nature Scientific Reports. BERLIN: NATURE PORTFOLIO, 2024, roč. 14, č. 1, s. 1-17. ISSN 2045-2322. Dostupné z: https://doi.org/10.1038/s41598-024-60030-9.

@article{2481438,
   author = {Kunova, Nina and Ondrovicova, Gabriela and Bauer, Jacob A and Krajcovicova, Veronika and Pinkas, Matyáš and Stojkovicova, Barbora and Havalova, Henrieta and Lukacova, Veronika and Kohutova, Lenka and Kostan, Julius and Martinakova, Lucia and Barath, Peter and Nováček, Jiří and Zoll, Sebastian and Kereiche, Sami and Kutejova, Eva and Pevala, Vladimir},
   article_location = {BERLIN},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41598-024-60030-9},
   keywords = {COMPUTED-TOMOGRAPHY; IMAGE-RECONSTRUCTION; CT},
   language = {eng},
   issn = {2045-2322},
   journal = {Nature Scientific Reports},
   title = {Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions},
   url = {https://www.nature.com/articles/s41598-024-60030-9},
   volume = {14},
   year = {2024}
}

TY  - JOUR
ID  - 2481438
AU  - Kunova, Nina - Ondrovicova, Gabriela - Bauer, Jacob A - Krajcovicova, Veronika - Pinkas, Matyáš - Stojkovicova, Barbora - Havalova, Henrieta - Lukacova, Veronika - Kohutova, Lenka - Kostan, Julius - Martinakova, Lucia - Barath, Peter - Nováček, Jiří - Zoll, Sebastian - Kereiche, Sami - Kutejova, Eva - Pevala, Vladimir
PY  - 2024
TI  - Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions
JF  - Nature Scientific Reports
VL  - 14
IS  - 1
SP  - 1-17
EP  - 1-17
PB  - NATURE PORTFOLIO
SN  - 20452322
KW  - COMPUTED-TOMOGRAPHY
KW  - IMAGE-RECONSTRUCTION
KW  - CT
UR  - https://www.nature.com/articles/s41598-024-60030-9
N2  - Phosphorylation plays a crucial role in the regulation of many fundamental cellular processes. Phosphorylation levels are increased in many cancer cells where they may promote changes in mitochondrial homeostasis. Proteomic studies on various types of cancer identified 17 phosphorylation sites within the human ATP-dependent protease Lon, which degrades misfolded, unassembled and oxidatively damaged proteins in mitochondria. Most of these sites were found in Lon's N-terminal (NTD) and ATPase domains, though little is known about the effects on their function. By combining the biochemical and cryo-electron microscopy studies, we show the effect of Tyr186 and Tyr394 phosphorylations in Lon's NTD, which greatly reduce all Lon activities without affecting its ability to bind substrates or perturbing its tertiary structure. A substantial reduction in Lon's activities is also observed in the presence of polyphosphate, whose amount significantly increases in cancer cells. Our study thus provides an insight into the possible fine-tuning of Lon activities in human diseases, which highlights Lon's importance in maintaining proteostasis in mitochondria.
ER  -

KUNOVA, Nina; Gabriela ONDROVICOVA; Jacob A BAUER; Veronika KRAJCOVICOVA; Matyáš PINKAS; Barbora STOJKOVICOVA; Henrieta HAVALOVA; Veronika LUKACOVA; Lenka KOHUTOVA; Julius KOSTAN; Lucia MARTINAKOVA; Peter BARATH; Jiří NOVÁČEK; Sebastian ZOLL; Sami KEREICHE; Eva KUTEJOVA a Vladimir PEVALA. Polyphosphate and tyrosine phosphorylation in the N-terminal domain of the human mitochondrial Lon protease disrupts its functions. \textit{Nature Scientific Reports}. BERLIN: NATURE PORTFOLIO, 2024, roč.~14, č.~1, s.~1-17. ISSN~2045-2322. Dostupné z: https://doi.org/10.1038/s41598-024-60030-9.

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