Characterization, design, and function of the mitochondrial proteome: from organs to organisms.
Mitochondria are a common energy source for organs and organisms; their diverse functions are specialized according to the unique phenotypes of their hosting environment. Perturbation of mitochondrial homeostasis accompanies significant pathological phenotypes. However, the connections between mitochondrial proteome properties and function remain to be experimentally established on a systematic level. This uncertainty impedes the contextualization and translation of proteomic data to the molecular derivations of mitochondrial diseases. We present a collection of mitochondrial features and functions from four model systems, including two cardiac mitochondrial proteomes from distinct genomes (human and mouse), two unique organ mitochondrial proteomes from identical genetic codons (mouse heart and mouse liver), as well as a relevant metazoan out-group (drosophila). The data, composed of mitochondrial protein abundance and their biochemical activities, capture the core functionalities of these mitochondria. This investigation allowed us to redefine the core mitochondrial proteome from organs and organisms, as well as the relevant contributions from genetic information and hosting milieu. Our study has identified significant enrichment of disease-associated genes and their products. Furthermore, correlational analyses suggest that mitochondrial proteome design is primarily driven by cellular environment. Taken together, these results connect proteome feature with mitochondrial function, providing a prospective resource for mitochondrial pathophysiology and developing novel therapeutic targets in medicine.
Departments of Physiology and Medicine/Division of Cardiology, David Geffen School of Medicine at UCLA , 675 Charles E. Young Drive, MRL Building, Suite 1609, Los Angeles, California 90095, United States.
Christopher
C
Lotz
Amanda J
AJ
Lin
Caitlin M
CM
Black
Jun
J
Zhang
Edward
E
Lau
Ning
N
Deng
Yueju
Y
Wang
Nobel C
NC
Zong
Jeong H
JH
Choi
Tao
T
Xu
David A
DA
Liem
Paavo
P
Korge
James N
JN
Weiss
Henning
H
Hermjakob
John R
JR
Yates
Rolf
R
Apweiler
Peipei
P
Ping
D000818:Animals; D002853:Chromatography, Liquid; D004331:Drosophila melanogaster; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D051379:Mice; D024101:Mitochondrial Proteins / Q000378:metabolism*; D020543:Proteome; D053719:Tandem Mass Spectrometry
D024101:Mitochondrial Proteins; D020543:Proteome