Systems biochemistry approaches to defining mitochondrial protein function
Recent efforts—including our MitoCarta work—have provided a map of mitochondrial proteins and their sub-mitochondrial locations. Yet, hundreds of these proteins remain poorly characterized, limiting our understanding of basic mitochondrial function and pathophysiology. To address this, we are blending modern large-scale and classical reductionist approaches—a process we refer to as ‘‘systems biochemistry’’—to link these mitochondrial uncharacterized (x) proteins (MXPs) to specific pathways and processes. This work is helping to identify new disease-related mitochondrial proteins and long-sought ‘‘missing’’ proteins that fulfill key functions. Collectively, these studies are moving us toward a more complete understanding of mitochondrial activities and providing a molecular framework for the investigation of mitochondrial pathogenesis.
Selected Recent Publications
- Systematic analysis of NDUFAF6 in complex I assembly and mitochondrial disease
Sung AY, Guerra RM, Steenberge LH, Alston CL, Murayama K, Okazaki Y, Shimura M, Prokisch H, Ghezzi D, Torraco A, Carrozzo R, Rötig A, Taylor RW, Keck JL, and Pagliarini DJ
Nature Metabolism 2024 - Defining mitochondrial protein functions through deep multiomic profiling
Rensvold JW*, Shishkova E*, Miller IJ, Sverchkov Y, Cetinkaya A, Pyle A, Manicki M, Brademan DR, Alanay Y, Raiman J, Jochem J, Peters SR, Linke V, Hutchins PD, Overmyer KA, Salome AZ, Hebert AS, Balnis CV, Kwiecien NW, Rush MJ, Westphall MS, Craven M, Akarsu NA, Taylor RW, Coon JJ†, and Pagliarini DJ†
Nature, 2022 doi: 10.1038/s41586-022-04765-3 - Systems biochemistry approaches to defining mitochondrial protein function
Sung AY, Floyd BJ, and Pagliarini DJ
Cell Metabolism, 2020 31(4):669-678 - Systems analyses reveal physiological roles and genetic regulators of liver lipid species
Jha P*, McDevitt MT*, Gupta R*, Quiros PM, Williams EG, Gariani K, Sleiman MB, Diserens L, Jochem A, Ulbrich A, Coon JJ, Auwerx J†, and Pagliarini DJ†
Cell Systems, 2018 6(6):722-733 - Multi-omic mitoprotease profiling defines a role for Oct1p in coenzyme Q production
Veling MT, Reidenbach AG, Freiberger EC, Kwiecien NW, Hutchins PD, Drahnak MJ, Jochem A, Ulbrich A, Rush JPR, Russell JD, Coon JJ, and Pagliarini DJ
Molecular Cell, 2017 Dec 7 PMID: 29220658 - Mitochondrial Protein Functions Elucidated by Multi-Omic Mass Spectrometry Profiling
Stefely JA*, Kwiecien NW*, Freiberger EC, Richards AL, Jochem A, Rush MJ, Ulbrich A, Robinson KP, Hutchins PD, Veiling MT, Guo X, Kemmerer ZA, Connors KJ, Trujillo EA, Sokol J, Marx H, Westphall MS, Hebert AS, Pagliarini DJ†, Coon JJ†
Nature Biotechnology, 2016 34(11):1191-1197
PREVIEW - Mitochondrial Protein Interaction Mapping Identifies Regulators of Respiratory Chain Function
Floyd BJ*, Wilkerson EM*, Veling MT*, Minogue CE*, Xia C, Beebe ET, Wrobel RL, Cho H, Kremer LS, Alston CL, Gromek KA, Dolan BK, Ulbrich A, Stefely JA, Bohl SL, Werner KM, Jochem A, Westphall MS, Rensvold JW, Taylor RW, Prokisch H, Kim JJ, Coon JJ, Pagliarini DJ
Molecular Cell, 2016 Aug 18;63(4):621-32
Return to Research Overview page
Elucidating the mechanisms of coenzyme Q biosynthesis
Regulation of mitochondrial function and biogenesis