The Energetic State of Mitochondria Modulates Complex III Biogenesis through the ATP-Dependent Activity of Bcs1

• DOI: 10.1016/j.cmet.2013.08.017
• Publication Date: 2013-09-19T16:01:32Z
• Authors: Jelena Ostojić; Cristina Panozzo; Jean-Paul Lasserre; Cécile Nouet; Florence Courtin; Corinne Blancard; Jean-Paul di Rago; Geneviève Dujardin
• Keywords: 0303 health sciences; Saccharomyces cerevisiae Proteins; Physiology; Membrane Proteins; [SDV.BC]Life Sciences [q-bio]/Cellular Biology; Cell Biology; Saccharomyces cerevisiae; Mitochondria; Protein Structure, Tertiary; ATP Synthetase Complexes; Mitochondrial Proteins; Electron Transport Complex III; 03 medical and health sciences; Adenosine Triphosphate; Mitochondrial Membranes; Mutation; ATPases Associated with Diverse Cellular Activities; Molecular Biology; Molecular Chaperones

Our understanding of the mechanisms involved in mitochondrial biogenesis has continuously expanded during the last decades, yet little is known about how they are modulated to optimize the functioning of mitochondria. Here, we show that mutations in the ATP binding domain of Bcs1, a chaperone involved in the assembly of complex III, can be rescued by mutations that decrease the ATP hydrolytic activity of the ATP synthase. Our results reveal a Bcs1-mediated control loop in which the biogenesis of complex III is modulated by the energy-transducing activity of mitochondria. Although ATP is well known as a regulator of a number of cellular activities, we show here that ATP can be also used to modulate the biogenesis of an enzyme by controlling a specific chaperone involved in its assembly. Our study further highlights the intramitochondrial adenine nucleotide pool as a potential target for the treatment of Bcs1-based disorders.