Mitochondrial biogenesis and the role of the protein import pathway

  • Hood D
  • Adhihetty P
  • Colavecchia M
 et al. 
  • 20

    Readers

    Mendeley users who have this article in their library.
  • 37

    Citations

    Citations of this article.

Abstract

PURPOSE: The importance of the mitochondrial protein import pathway, discussed relative to other steps involved in the overall biogenesis of the organelle, are reviewed.

RESULTS: Mitochondrial biogenesis is a product of complex interactions between the nuclear and mitochondrial genomes. Signaling pathways, such as those activated by exercise, initiate the activation of transcription factors that increase the production of mRNA from nuclear and mitochondrial DNA. Nuclear gene products are translated in the cytosol as precursor proteins with inherent targeting signals. These precursor proteins interact with molecular chaperones that direct them to the import machinery of the outer membrane (Tom complex). The precursor is unfolded and transferred through the outer membrane, across the intermembrane space to the mitochondrial inner membrane translocases (Tim complex). Intramitochondrial components (mtHSP70) pull the precursor into the matrix, cleave off the targeting sequence (mitochondrial processing peptidase), and refold the protein (HSP60, cpn10) into its mature conformation. Physiological stressors such as contractile activity and thyroid hormone accelerate protein import into the mitochondria, coincident with an increase in the expression of some components of the import machinery. This is important for the overall expansion of the mitochondrial reticulum. Conversely, impairments in the import process can be a cause of mitochondrial dysfunction and disease.

CONCLUSIONS: Efforts to further characterize the components of the import machinery, to define the role of specific machinery components on the import rate, and to examine protein import function in a variety of mitochondrial diseases are warranted.

Author-supplied keywords

  • Exercise
  • Gene transcription
  • Heat-shock proteins
  • Mitochondrial DNA
  • Mitochondrial disease
  • Skeletal muscle

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • David A. Hood

  • Peter J. Adhihetty

  • Marco Colavecchia

  • Joseph W. Gordon

  • Isabella Irrcher

  • Anna Maria Joseph

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free