Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria

Vamsi K Mootha; Jakob Bunkenborg; Jesper V Olsen; Majbrit Hjerrild; Jacek R Wisniewski; Erich Stahl; Marjan S Bolouri; Heta N Ray; Smita Sihag; Michael Kamal; Nick Patterson; Eric S Lander; Matthias Mann

Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria

Vamsi K Mootha, Jakob Bunkenborg, Jesper V Olsen, Majbrit Hjerrild, Jacek R Wisniewski, Erich Stahl, Marjan S Bolouri, Heta N Ray, Smita Sihag, Michael Kamal, Nick Patterson, Eric S Lander, Matthias Mann

683 Citations (Scopus)

Abstract

Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger "neighborhood" of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.

Original language	English
Journal	Cell
Volume	115
Issue number	5
Pages (from-to)	629-40
Number of pages	11
ISSN	0092-8674
Publication status	Published - 2003
Externally published	Yes

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Cite this

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title = "Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria",

abstract = "Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger {"}neighborhood{"} of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.",

author = "Mootha, {Vamsi K} and Jakob Bunkenborg and Olsen, {Jesper V} and Majbrit Hjerrild and Wisniewski, {Jacek R} and Erich Stahl and Bolouri, {Marjan S} and Ray, {Heta N} and Smita Sihag and Michael Kamal and Nick Patterson and Lander, {Eric S} and Matthias Mann",

note = "Keywords: Animals; Cell Line; Cell Respiration; DNA Fingerprinting; DNA, Mitochondrial; Gene Expression Regulation, Enzymologic; Humans; Male; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Phosphorylation; Proteomics; RNA, Messenger",

year = "2003",

language = "English",

volume = "115",

pages = "629--40",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

T1 - Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria

AU - Mootha, Vamsi K

AU - Bunkenborg, Jakob

AU - Olsen, Jesper V

AU - Hjerrild, Majbrit

AU - Wisniewski, Jacek R

AU - Stahl, Erich

AU - Bolouri, Marjan S

AU - Ray, Heta N

AU - Sihag, Smita

AU - Kamal, Michael

AU - Patterson, Nick

AU - Lander, Eric S

AU - Mann, Matthias

N1 - Keywords: Animals; Cell Line; Cell Respiration; DNA Fingerprinting; DNA, Mitochondrial; Gene Expression Regulation, Enzymologic; Humans; Male; Mice; Mitochondria; Mitochondrial Proteins; Oxidative Phosphorylation; Proteomics; RNA, Messenger

PY - 2003

Y1 - 2003

N2 - Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger "neighborhood" of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.

AB - Mitochondria are tailored to meet the metabolic and signaling needs of each cell. To explore its molecular composition, we performed a proteomic survey of mitochondria from mouse brain, heart, kidney, and liver and combined the results with existing gene annotations to produce a list of 591 mitochondrial proteins, including 163 proteins not previously associated with this organelle. The protein expression data were largely concordant with large-scale surveys of RNA abundance and both measures indicate tissue-specific differences in organelle composition. RNA expression profiles across tissues revealed networks of mitochondrial genes that share functional and regulatory mechanisms. We also determined a larger "neighborhood" of genes whose expression is closely correlated to the mitochondrial genes. The combined analysis identifies specific genes of biological interest, such as candidates for mtDNA repair enzymes, offers new insights into the biogenesis and ancestry of mammalian mitochondria, and provides a framework for understanding the organelle's contribution to human disease.

M3 - Journal article

C2 - 14651853

SN - 0092-8674

VL - 115

SP - 629

EP - 640

JO - Cell

JF - Cell

IS - 5

ER -