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A single mitochondrion is a bean-shaped organelle enclosed by a double-membrane system. The outer membrane of mitochondria is smooth and contains many porins - the integral membrane transporters. Porins enable free diffusion of ions and small uncharged molecules through the outer mitochondrial membrane but limit the transport of molecules larger than 5000 Daltons. Further, the outer mitochondrial membrane forms a unique structure called membrane contact sites with other subcellular organelles,...
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Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death.  Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
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Quantitative high-confidence human mitochondrial proteome and its dynamics in cellular context.

Marcel Morgenstern1, Christian D Peikert1, Philipp Lübbert2

  • 1Institute of Biology II, Biochemistry and Functional Proteomics, Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.

Cell Metabolism
|November 20, 2021
PubMed
Summary

Researchers defined a high-confidence human mitochondrial proteome (MitoCoP) of over 1,100 proteins. This resource aids understanding of mitochondrial dynamics, functions, and diseases, particularly in the central nervous system and metabolism.

Keywords:
Mitochondriacomplexomecopy numbersdiseasehalf-liveshigh-confidence proteomehuman cellsprotein translocationrespiratory chainsmORFs

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Mitochondria are crucial organelles involved in cellular energy production, metabolism, signaling, and quality control.
  • Mitochondrial dysfunction is implicated in numerous human diseases.
  • The precise composition of the human mitochondrial proteome remains incompletely defined.

Purpose of the Study:

  • To establish a high-confidence human mitochondrial proteome (MitoCoP).
  • To characterize the abundance, dynamics, and disease associations of mitochondrial proteins.
  • To provide a comprehensive resource for mitochondrial research.

Main Methods:

  • Classification of over 8,000 proteins from human cell mitochondrial preparations.
  • Identification of protein interactors involved in mitochondrial translocases, respiratory chain, and ATP synthase assembly.
  • Analysis of MitoCoP protein abundance, dynamics (half-lives), and gene-disease associations.

Main Results:

  • Defined a high-confidence mitochondrial proteome (MitoCoP) comprising >1,100 proteins.
  • MitoCoP proteins constitute approximately 7% of the cellular proteome, with HSP60-HSP10 chaperones being most abundant.
  • MitoCoP exhibits dynamics spanning three orders of magnitude (half-lives from hours to months), indicating rapid regulation.
  • 460 MitoCoP genes are linked to human diseases, with a notable prevalence in central nervous system and metabolic disorders.

Conclusions:

  • The MitoCoP provides a robust, high-confidence dataset for human mitochondrial proteins.
  • This resource facilitates a deeper understanding of mitochondrial protein dynamics, function, and their roles in disease.
  • MitoCoP serves as a valuable tool for future research into mitochondrial biology and pathology.