A new mechanism of ATP synthase subunit 6 and 9 translation regulation by their assembly in yeast mitochondria

• Published in: Biochimica et biophysica acta. Bioenergetics 2022-09, Vol.1863, p.148786, Article 148786
• Main Authors: Kabala, Anna, Binko, Krystyna, Godard, Francois, Dautant, Alain, Baranowska, Emilia, Skoczen, Natalia, Gombeau, Kevin, Bouhier, Marine, Becker, Hubert, Ackerman, Sharon, Steinmetz, Lars, Tribouillard-Tanvier, Deborah, Kucharczyk, Roza, di Rago, Jean-Paul
• Format: Article
• Language: English
• Subjects: Biochemistry, Molecular Biology; Life Sciences; Molecular biology
• ISSN: 0005-2728; 1879-2650
• DOI: 10.1016/j.bbabio.2022.148786

The yeast mitochondrial ATP synthase is composed of 17 subunits, assembled in different stoichiometry, of which 3 (subunits 6, 8, and 9) are encoded by mitochondrial genes while the 14 others have a nuclear genetic origin. Within the membrane domain (FO) of this enzyme, the subunit 6 and a ring of 10 identical subunits 9 transport protons across the mitochondrial inner membrane coupled to ATP synthesis in the extra-membrane structure (F1) of ATP synthase. As a result of their dual genetic origin, the ATP synthase subunits are synthesized in the cytosol and inside the mitochondrion. The mechanisms that prevent unbalanced production of ATP synthase subunits are poorly understood. We show that the rate of translation of the subunits 9 and 6 is enhanced in strains with mutations leading to specific defects in the assembly of these proteins. We show that the translational regulation of subunit 6 involves several components of ATP synthase, at least the F1 and subunit 9, the chaperoning activities of two proteins (Atp10 and Atp23) that are required to assemble subunit 6, and the 5'UTR of ATP6 mRNA, as a means to couple the synthesis of this protein to its incorporation into ATP synthase. Subunit 9 of ATP synthase is also subject to such a mechanism. The subunit 9 translation is correlated with its oligomerization into the ring. Three proteins (Aep1, Aep2 and a fragment of Atp25) required to express subunit 9, the F1, and a protein (Phb1) are involved in the stabilization of newly synthesized subunit 9. These assembly-dependent feedback loops are important to coordinate the mitochondrialy encoded ATP synthase subunits expression with their assembly to the complex and under the control of nuclear-encoded subunits.