An ability to comprehensively track the assembly intermediates (AIs) of complex I (CI) biogenesis in Drosophila will enable the characterization of the precise mechanism(s) by which various CI regulators modulate CI assembly. Accordingly, we generated 21 novel antibodies to various mitochondrial proteins and used this resource to characterize the mechanism by which apoptosis-inducing factor (AIF) regulates CI biogenesis by tracking the AI profile observed when AIF expression is impaired. We find that when the AIF–Mia40 translocation complex is disrupted, the part of CI that transfers electrons to ubiquinone is synthesized but fails to progress in the CI biosynthetic pathway. This is associated with a reduction in intramitochondrial accumulation of the Mia40 substrate, MIC19. Importantly, knockdown of either MIC19 or MIC60, components of the mitochondrial contact site and cristae organizing system (MICOS), fully recapitulates the AI profile observed when AIF is inhibited. Thus, AIF’s effect on CI assembly is principally due to compromised intramitochondrial transport of the MICOS complex.

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Traditional underrepresented minority (URM) groups (African Americans, Hispanic Americans, Native Americans) remain underrepresented among physician-scientists. To address the dearth of URM physician-scientists, in 1993 the Weill Cornell/Rockefeller/Sloan Kettering Tri-Institutional MD-PhD Program developed a pipeline program, Gateways to the Laboratory (Gateways), which focuses on increasing the breadth and depth of the URM physician-scientist pipeline by offering an all-encompassing summer research training program which mirrors the life of a physician-scientist. This includes hypothesis-driven research and clinical shadowing opportunities, coupled with weekly career development workshops and extensive multitiered mentoring. Among the 245 alumni who had "graduated" from Gateways as of 2013, 88% have pursued or completed advanced degrees. Among these, 74% completed or are pursuing MD, PhD, or MD-PhD degrees; and 17% completed or are pursuing combined MD-PhD degrees, over one-third of whom are enrolled in the Tri-Institutional MD-PhD Program. Gateways outcomes are compared to other programs with similar missions, which shows that Gateways has been successful at preparing URMs for MD-PhD Programs. The program serves as a model for how to increase the national pool of competitive URM MD-PhD applicants.