Sit4p-mediated dephosphorylation of Atp2p regulates ATP synthase activity and mitochondrial function

• Type: Article in International Scientific Journal
• Date: 2018

Authors

Pereira, C (Author) Other; Pereira, AT (Author) Other; Osorio, H (Author) Other; Moradas Ferreira, P (Author) Other; Vitor Costa (Author) ICBAS

Journal

Title: Biochimica et Biophysica Acta - Bioenergetics

Vol. 1859

Pages: 591-601

ISSN: 0005-2728

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 6 Citations

Other information

Authenticus ID: P-00R-A7D

DOI: 10.1016/j.bbabio.2018.04.011

Abstract (EN): Sit4p is a type 2A-related protein phosphatase in Saccharomyces cerevisiae involved in a wide spectrum of cellular functions, including the glucose repression of mitochondrial transcription. Here we report that Sit4p is also involved in post-translational regulation of mitochondrial proteins and identified 9 potential targets. One of these, the ATP synthase (FoF1 complex) beta subunit Atp2p, was characterized and two phosphorylation sites, T124 and T317, were identified. Expression of Atp2p-T124 or T317 phosphoresistant versions in sit44 cells decreased Atp2p phosphorylation confirming these as Sit4p-regulated sites. Moreover, Sit4p and Atp2p interacted both physically and genetically. Mimicking phosphorylation at T124 or T317 increased Atp2p levels, resulting in higher abundance/activity of ATP synthase. Similar changes were observed in sit44 cells in which Atp2p is endogenously more phosphorylated. Expression of Atp2-T124 or T317 phosphomimetics also increased mitochondrial respiration and ATP levels and extended yeast lifespan. These results suggest that Sit4p-mediated dephosphorylation of Atp2p-T124/T317 downregulates Atp2p alongside with ATP synthase and mitochondrial function. Combination of transcriptional with post-translational regulation during fermentative growth may allow for a more efficient Sit4p repression of mitochondrial respiration.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11