Mitochondrial biogenesis and the role of the protein import pathway.
OBJECTIVE
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.
Hood
David A
DA
School of Kinesiology and Health Science, Department of Biology, York University, Toronto, Ontario, Canada. dhood@yorku.ca
Adhihetty
Peter J
PJ
Colavecchia
Marco
M
Gordon
Joseph W
JW
Irrcher
Isabella
I
Joseph
Anna-Maria
AM
Lowe
Sabena T
ST
Rungi
Arne A
AA
D002352:Carrier Proteins / Q000378:metabolism; D019069:Cell Respiration / Q000502:physiology; D018834:Chaperonin 60 / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D015444:Exercise / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology; D006801:Humans; D008931:Mitochondria, Muscle / Q000378:metabolism*; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018832:Molecular Chaperones / Q000378:metabolism; D009119:Muscle Contraction / Q000502:physiology; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology; D014178:Translocation, Genetic / Q000502:physiology
D002352:Carrier Proteins; D018834:Chaperonin 60; D018840:HSP70 Heat-Shock Proteins; D033681:Mitochondrial Membrane Transport Proteins; D000090622:Mitochondrial Precursor Protein Import Complex Proteins; D024101:Mitochondrial Proteins; D018832:Molecular Chaperones; D011498:Protein Precursors