title: Systematic characterization of the murine mitochondrial proteome using functionally validated cardiac mitochondria.
abstract: Mitochondria play essential roles in cardiac pathophysiology and the murine model has been extensively used to investigate cardiovascular diseases. In the present study, we characterized murine cardiac mitochondria using an LC/MS/MS approach. We extracted and purified cardiac mitochondria; validated their functionality to ensure the final preparation contains necessary components to sustain their normal function; and subjected these validated organelles to LC/MS/MS-based protein identification. A total of 940 distinct proteins were identified from murine cardiac mitochondria, among which, 480 proteins were not previously identified by major proteomic profiling studies. The 940 proteins consist of functional clusters known to support oxidative phosphorylation, metabolism, and biogenesis. In addition, there are several other clusters, including proteolysis, protein folding, and reduction/oxidation signaling, which ostensibly represent previously under-appreciated tasks of cardiac mitochondria. Moreover, many identified proteins were found to occupy other subcellular locations, including cytoplasm, ER, and golgi, in addition to their presence in the mitochondria. These results provide a comprehensive picture of the murine cardiac mitochondrial proteome and underscore tissue- and species-specification. Moreover, the use of functionally intact mitochondria insures that the proteomic observations in this organelle are relevant to its normal biology and facilitates decoding the interplay between mitochondria and other organelles.
authors.affiliation: Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Xiaohai
authors.initials: X
authors.lastname: Li
authors.forename: Michael
authors.initials: M
authors.lastname: Mueller
authors.forename: Yueju
authors.initials: Y
authors.lastname: Wang
authors.forename: Chenggong
authors.initials: C
authors.lastname: Zong
authors.forename: Ning
authors.initials: N
authors.lastname: Deng
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Vondriska
authors.forename: David A
authors.initials: DA
authors.lastname: Liem
authors.forename: Jeong-In
authors.initials: JI
authors.lastname: Yang
authors.forename: Paavo
authors.initials: P
authors.lastname: Korge
authors.forename: Henry
authors.initials: H
authors.lastname: Honda
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Rolf
authors.initials: R
authors.lastname: Apweiler
authors.forename: Peipei
authors.initials: P
authors.lastname: Ping
mesh_terms: D000818:Animals; D006801:Humans; D015151:Immunoblotting; D013058:Mass Spectrometry; D051379:Mice; D008929:Mitochondria, Heart / Q000737:chemistry*; D024101:Mitochondrial Proteins / Q000032:analysis*; D010101:Oxygen Consumption; D020543:Proteome / Q000032:analysis*
chemical_list: D024101:Mitochondrial Proteins; D020543:Proteome