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.

Deficiency in parvalbumin, but not in calbindin D-28k upregulates mitochondrial volume and decreases smooth endoplasmic reticulum surface selectively in a peripheral, subplasmalemmal region in the soma of Purkinje cells

“…Design-based, unbiased morphometry revealed a global 40% increase in mitochondrial volume density in PVϪ/Ϫ PC somata. Since mitochondria display a large heterogeneity in terms of composition, structure, intracellular localization and function (Meldolesi, 2001;Park et al, 2001;Collins et al, 2002;Mootha et al, 2003), we conjectured that upregulation of mitochondria might be non-random in the PC somata, concentrated at sites of principal Ca 2ϩ entry. Steep elevations of [Ca 2ϩ ] i with a half-rise time of 50 ms confined to a submembrane shell of 2-to 3-m thickness occur after single climbing fiber stimulation (Eilers et al, 1995).…”

Application of capillary isotachophoresis‐based multidimensional separations coupled with electrospray ionization‐tandem mass spectrometry for characterization of mouse brain mitochondrial proteome

“…Consequently, considerable efforts have been devoted to the application of various LC techniques in single or multidimensional separation format prior to MS detection for the analysis of mitochondrial proteins [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. In particular, the peptide-based shotgun proteomic studies fully exploit the resolution and sensitivity achievable with multidimensional LC-MS or SDS-PAGE/LC-MS approaches, allowing many additional mitochondrial proteins to be identified.…”

Proteomic survey towards the tissue-specific proteins of mouse mitochondria

“…Since the turn of the century, proteomic approaches have expedited protein research, including the identification of proteins present in various tissues and organelles [12]. Using shotgun tryptic-digestion and LC MS/MS, Mann's group screened mitochondrial proteins obtained from the mouse brain, heart, kidney and liver [13]. In total, 399 mitochondrial proteins were identified, in which approximately 50% were not generally detected in all the tissues.…”