DNA Repair Protein APE1 Degrades Dysfunctional Abasic mRNA in Mitochondria Affecting Oxidative Phosphorylation

被引：18

作者：

Barchiesi, Arianna ^{[1
]}

Bazzani, Veronica ^{[1
]}

Jabczynska, Agata ^{[2
]}

Borowski, Lukasz S. ^{[2
,3
]}

Oeljeklaus, Silke ^{[4
]}

Warscheid, Bettina ^{[4
,5
,6
]}

Chacinska, Agnieszka ^{[7
,8
]}

Szczesny, Roman J. ^{[2
]}

Vascotto, Carlo ^{[1
,7
]}

机构：

[1] Univ Udine, Dept Med, I-33100 Udine, Italy

[2] Polish Acad Sci, Inst Biochem & Biophys, Pawinskiego 5A, PL-02106 Warsaw, Poland

[3] Univ Warsaw, Fac Biol, Inst Genet & Biotechnol, Pawinskiego 5A, PL-02106 Warsaw, Poland

[4] Univ Freiburg, Fac Biol, Inst Biol 2, Biochem & Funct Prote, D-79104 Freiburg, Germany

[5] Univ Freiburg, Signalling Res Ctr BIOSS, Freiburg, Germany

[6] Univ Freiburg, Signalling Res Ctr CIBSS, Freiburg, Germany

[7] Univ Warsaw, Ctr New Technol, Lab Mitochondria Biogenesis, PL-02097 Warsaw, Poland

[8] Univ Warsaw, Ctr New Technol, ReMedy Int Res Agenda Unit, PL-02097 Warsaw, Poland

来源：

JOURNAL OF MOLECULAR BIOLOGY | 2021年 / 433卷 / 18期

基金：

欧洲研究理事会;

关键词：

mitochondria; apurinic/apyrimidinic endonuclease 1; RNA processing; oxidative phosphorylation; HUMAN APURINIC ENDONUCLEASE; BASE EXCISION-REPAIR; BINDING ACTIVITY; COMPLEX-I; IDENTIFICATION; REF-1; QUANTIFICATION; STABILITY; MAINTAINS; APOPTOSIS;

D O I：

10.1016/j.jmb.2021.167125

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

APE1 is a multifunctional protein which plays a central role in the maintenance of nuclear and mitochondrial genomes repairing DNA lesions caused by oxidative and alkylating agents. In addition, it works as a redox signaling protein regulating gene expression by interacting with many transcriptional factors. Apart from these canonical activities, recent studies have shown that APE1 is also enzymatically active on RNA molecules. The present study unveils for the first time a new role of the mitochondrial form of APE1 protein in the metabolism of RNA in mitochondria. Our data demonstrate that APE1 is associated with mitochondrial messenger RNA and exerts endoribonuclease activity on abasic sites. Loss of APE1 results in the accumulation of damaged mitochondrial mRNA species, determining impairment in protein translation and reduced expression of mitochondrial-encoded proteins, finally leading to less efficient mitochondrial respiration. Altogether, our data demonstrate that APE1 plays an active role in the degradation of the mitochondrial mRNA and has a profound impact on mitochondrial well-being. (C) 2021 The Author(s). Published by Elsevier Ltd.

引用

页数：21

共 69 条

[11] The MIQE Guidelines: Minimum Information for Publication of Quantitative Real-Time PCR Experiments [J].