Bradley, Michelle

Michelle is a student in the Biochemistry, Molecular and Structural Biology Graduate Program, where she works in the laboratory of Dr. Cathy Clarke.  She joined the CMB training program in 2016.  She received a B.A. degree in 2015 from Colgate University.

Mentor: Dr. Cathy Clarke

Research project:

Coenzyme Q, also known as ubiquinone or Q, is an essential electron carrier that operates within the mitochondrial electron transport chain (ETC). Saccharomyces cerevisiae Q6 biosynthesis is localized to the mitochondria, where thirteen known mitochondrial proteins drive the formation of Q6: Coq1-Coq11, Yah1, and Arh1. Several of the aforementioned proteins (Coq3-Coq9, Coq11) required for efficient Q6 biosynthesis organize into a high molecular weight complex positioned at the inner mitochondrial membrane, as part of what has been designated as the ‘CoQ-synthome’. A recent paper by the Clarke laboratory identified Coq11 as a novel CoQ-synthome polypeptide that co-purified with CNAP-tagged Coq4, Coq5, and Coq7. It was further shown to be essential for efficient de novo Q6 biosynthesis through the study of coq11 null mutants. However, the functional role, organization, and stoichiometry of Coq11 within the CoQ-synthome have yet to be realized.

My research involves the study of the role of Coq11 in Q6 biosynthesis, with the ultimate goal being to investigate its human homolog (NDUFA9). I will first generate a monoclonal antibody to Coq11 in order to determine sub-mitochondrial localization and identify its binding partners. Rescue assays of Q6 in coq11 null mutants by supplementation of exogenous NDUFA9 will further establish the relationship between yeast and human Q synthesis. With about 20% sequence homology to Coq11, NDUFA9 is particularly interesting due to its positioning at complex I in the ETC, while no other Coq polypeptide shows this type of localization. Analysis of Q precursors and final Q6 levels by mass spectrometry will provide powerful insights into the Q biosynthetic pathway towards the objective of designing effective disease therapeutics.