T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase

Nuclear-encoded Atp23 was previously shown to have dual functions, including processing the yeast Atp6 precursor and assisting the assembly of yeast mitochondrial ATP synthase. However, it remains unknown whether there are genes functionally complementary to <i>ATP23</i> to rescue <i&...

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Main Authors: Guangying Yang, Tong Zhao, Shan Lu, Jun Weng, Xiaomei Zeng
Format: Article
Language:English
Published: MDPI AG 2022-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/4/2327
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author Guangying Yang
Tong Zhao
Shan Lu
Jun Weng
Xiaomei Zeng
author_facet Guangying Yang
Tong Zhao
Shan Lu
Jun Weng
Xiaomei Zeng
author_sort Guangying Yang
collection DOAJ
description Nuclear-encoded Atp23 was previously shown to have dual functions, including processing the yeast Atp6 precursor and assisting the assembly of yeast mitochondrial ATP synthase. However, it remains unknown whether there are genes functionally complementary to <i>ATP23</i> to rescue <i>atp23</i> null mutant. In the present paper, we screen and characterize three revertants of <i>atp23</i> null mutant and reveal a T1121G point mutation in the mitochondrial gene <i>COX1</i> coding sequence, which leads to Val374Gly mutation in Cox1, the suppressor in the revertants. This was verified further by the partial restoration of mitochondrial ATP synthase assembly in <i>atp23</i> null mutant transformed with exogenous hybrid <i>COX1</i> <i>T1121G</i> mutant plasmid. The predicted tertiary structure of the Cox1 p.Val374Gly mutation showed no obvious difference from wild-type Cox1. By further chase labeling with isotope [<sup>35</sup>S]-methionine, we found that the stability of Atp6 of ATP synthase increased in the revertants compared with the <i>atp23</i> null mutant. Taking all the data together, we revealed that the T1121G point mutation of mitochondrial gene <i>COX1</i> could partially restore the unassembly of mitochondrial ATP synthase in <i>atp23</i> null mutant by increasing the stability of Atp6. Therefore, this study uncovers a gene that is partially functionally complementary to <i>ATP23</i> to rescue <i>ATP23</i> deficiency, broadening our understanding of the relationship between yeast the cytochrome c oxidase complex and mitochondrial ATP synthase complex.
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spelling doaj.art-cadefb06f8374f3dba559022b710927d2023-11-23T20:23:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234232710.3390/ijms23042327T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP SynthaseGuangying Yang0Tong Zhao1Shan Lu2Jun Weng3Xiaomei Zeng4Key Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaKey Laboratory of Molecular Biophysics of Chinese Ministry of Education, Center for Human Genome Research, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, ChinaNuclear-encoded Atp23 was previously shown to have dual functions, including processing the yeast Atp6 precursor and assisting the assembly of yeast mitochondrial ATP synthase. However, it remains unknown whether there are genes functionally complementary to <i>ATP23</i> to rescue <i>atp23</i> null mutant. In the present paper, we screen and characterize three revertants of <i>atp23</i> null mutant and reveal a T1121G point mutation in the mitochondrial gene <i>COX1</i> coding sequence, which leads to Val374Gly mutation in Cox1, the suppressor in the revertants. This was verified further by the partial restoration of mitochondrial ATP synthase assembly in <i>atp23</i> null mutant transformed with exogenous hybrid <i>COX1</i> <i>T1121G</i> mutant plasmid. The predicted tertiary structure of the Cox1 p.Val374Gly mutation showed no obvious difference from wild-type Cox1. By further chase labeling with isotope [<sup>35</sup>S]-methionine, we found that the stability of Atp6 of ATP synthase increased in the revertants compared with the <i>atp23</i> null mutant. Taking all the data together, we revealed that the T1121G point mutation of mitochondrial gene <i>COX1</i> could partially restore the unassembly of mitochondrial ATP synthase in <i>atp23</i> null mutant by increasing the stability of Atp6. Therefore, this study uncovers a gene that is partially functionally complementary to <i>ATP23</i> to rescue <i>ATP23</i> deficiency, broadening our understanding of the relationship between yeast the cytochrome c oxidase complex and mitochondrial ATP synthase complex.https://www.mdpi.com/1422-0067/23/4/2327<i>ATP23</i>revertant<i>COX1</i>point mutationmitochondrial ATP synthasestability of Atp6
spellingShingle Guangying Yang
Tong Zhao
Shan Lu
Jun Weng
Xiaomei Zeng
T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
International Journal of Molecular Sciences
<i>ATP23</i>
revertant
<i>COX1</i>
point mutation
mitochondrial ATP synthase
stability of Atp6
title T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
title_full T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
title_fullStr T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
title_full_unstemmed T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
title_short T1121G Point Mutation in the Mitochondrial Gene <i>COX1</i> Suppresses a Null Mutation in <i>ATP23</i> Required for the Assembly of Yeast Mitochondrial ATP Synthase
title_sort t1121g point mutation in the mitochondrial gene i cox1 i suppresses a null mutation in i atp23 i required for the assembly of yeast mitochondrial atp synthase
topic <i>ATP23</i>
revertant
<i>COX1</i>
point mutation
mitochondrial ATP synthase
stability of Atp6
url https://www.mdpi.com/1422-0067/23/4/2327
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