Signal presequences increase mitochondrial permeability and open the multiple conductance channel

Yulia E. Kushnareva, Maria L. Campo, Kathleen W. Kinnally, Patricia M. Sokolove

Research output: Contribution to journalArticle

Abstract

We have reported that the signal presequence of cytochrome oxidase subunit IV from Neurospora crassa increases the permeability of isolated rat liver mitochondria [P. M. Sokolove and K. W. Kinnally (1996) Arch. Biochem. Biophys. 336, 69] and regulates the behavior of the mutiple conductance channel (MCC) of yeast inner mitochondrial membrane [T. A. Lohret and K. W. Kinnally (1995) J. Biol. Chem. 270, 15950]. Here we examine in greater detail the action of a number of mitochondrial presequences from various sources and of several control peptides on the permeability of isolated rat liver mitochondria and on MCC activity monitored via patch-clamp techniques in both mammalian mitoplasts and a reconstituted yeast system. The data indicate that the ability to alter mitochondrial permeability is a property of most, but not all, signal peptides. Furthermore, it is clear that, although signal peptides are characterized by positive charge and the ability to form amphiphilic α helices, these two characteristics are not sufficient to guarantee mitochondrial effects. Finally, the results reveal a strong correlation between peptide effects on the permeability of isolated mitochondria and on MCC activity: peptides that induced swelling of mouse and rat mitochondria also activated the quiescent MCC of mouse mitoplasts and induced flickering of active MCC reconstituted from yeast mitochondrial membranes. Moreover, relative peptide efficacies were very similar for mitochondrial swelling and both types of patch-clamp experiments. We propose that patch-clamp recordings of MCC activity and the high-amplitude swelling induced by signal peptides reflect the opening of a single channel. Based on the selective responsiveness of that channel to signal peptides and the dependence of its opening in isolated mitochondria on membrane potential, we further suggest that the channel is involved in the mitochondrial protein import process.

Original languageEnglish (US)
Pages (from-to)107-115
Number of pages9
JournalArchives of Biochemistry and Biophysics
Volume366
Issue number1
DOIs
StatePublished - Jun 1 1999

Fingerprint

Mitochondria
Protein Sorting Signals
Permeability
Clamping devices
Peptides
Aptitude
Liver Mitochondrion
Yeasts
Yeast
Mitochondrial Membranes
Swelling
Rats
Membranes
Liver
Mitochondrial Swelling
Neurospora crassa
Flickering
Mitochondrial Proteins
Patch-Clamp Techniques
Electron Transport Complex IV

Keywords

  • Mitochondria
  • Multiple conductance channel
  • Permeability transition
  • Protein import
  • Signal peptides

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Signal presequences increase mitochondrial permeability and open the multiple conductance channel. / Kushnareva, Yulia E.; Campo, Maria L.; Kinnally, Kathleen W.; Sokolove, Patricia M.

In: Archives of Biochemistry and Biophysics, Vol. 366, No. 1, 01.06.1999, p. 107-115.

Research output: Contribution to journalArticle

Kushnareva, Yulia E. ; Campo, Maria L. ; Kinnally, Kathleen W. ; Sokolove, Patricia M. / Signal presequences increase mitochondrial permeability and open the multiple conductance channel. In: Archives of Biochemistry and Biophysics. 1999 ; Vol. 366, No. 1. pp. 107-115.
@article{713035ec605c4e36b47bcd382e5610c1,
title = "Signal presequences increase mitochondrial permeability and open the multiple conductance channel",
abstract = "We have reported that the signal presequence of cytochrome oxidase subunit IV from Neurospora crassa increases the permeability of isolated rat liver mitochondria [P. M. Sokolove and K. W. Kinnally (1996) Arch. Biochem. Biophys. 336, 69] and regulates the behavior of the mutiple conductance channel (MCC) of yeast inner mitochondrial membrane [T. A. Lohret and K. W. Kinnally (1995) J. Biol. Chem. 270, 15950]. Here we examine in greater detail the action of a number of mitochondrial presequences from various sources and of several control peptides on the permeability of isolated rat liver mitochondria and on MCC activity monitored via patch-clamp techniques in both mammalian mitoplasts and a reconstituted yeast system. The data indicate that the ability to alter mitochondrial permeability is a property of most, but not all, signal peptides. Furthermore, it is clear that, although signal peptides are characterized by positive charge and the ability to form amphiphilic α helices, these two characteristics are not sufficient to guarantee mitochondrial effects. Finally, the results reveal a strong correlation between peptide effects on the permeability of isolated mitochondria and on MCC activity: peptides that induced swelling of mouse and rat mitochondria also activated the quiescent MCC of mouse mitoplasts and induced flickering of active MCC reconstituted from yeast mitochondrial membranes. Moreover, relative peptide efficacies were very similar for mitochondrial swelling and both types of patch-clamp experiments. We propose that patch-clamp recordings of MCC activity and the high-amplitude swelling induced by signal peptides reflect the opening of a single channel. Based on the selective responsiveness of that channel to signal peptides and the dependence of its opening in isolated mitochondria on membrane potential, we further suggest that the channel is involved in the mitochondrial protein import process.",
keywords = "Mitochondria, Multiple conductance channel, Permeability transition, Protein import, Signal peptides",
author = "Kushnareva, {Yulia E.} and Campo, {Maria L.} and Kinnally, {Kathleen W.} and Sokolove, {Patricia M.}",
year = "1999",
month = "6",
day = "1",
doi = "10.1006/abbi.1999.1190",
language = "English (US)",
volume = "366",
pages = "107--115",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "1",

}

TY - JOUR

T1 - Signal presequences increase mitochondrial permeability and open the multiple conductance channel

AU - Kushnareva, Yulia E.

AU - Campo, Maria L.

AU - Kinnally, Kathleen W.

AU - Sokolove, Patricia M.

PY - 1999/6/1

Y1 - 1999/6/1

N2 - We have reported that the signal presequence of cytochrome oxidase subunit IV from Neurospora crassa increases the permeability of isolated rat liver mitochondria [P. M. Sokolove and K. W. Kinnally (1996) Arch. Biochem. Biophys. 336, 69] and regulates the behavior of the mutiple conductance channel (MCC) of yeast inner mitochondrial membrane [T. A. Lohret and K. W. Kinnally (1995) J. Biol. Chem. 270, 15950]. Here we examine in greater detail the action of a number of mitochondrial presequences from various sources and of several control peptides on the permeability of isolated rat liver mitochondria and on MCC activity monitored via patch-clamp techniques in both mammalian mitoplasts and a reconstituted yeast system. The data indicate that the ability to alter mitochondrial permeability is a property of most, but not all, signal peptides. Furthermore, it is clear that, although signal peptides are characterized by positive charge and the ability to form amphiphilic α helices, these two characteristics are not sufficient to guarantee mitochondrial effects. Finally, the results reveal a strong correlation between peptide effects on the permeability of isolated mitochondria and on MCC activity: peptides that induced swelling of mouse and rat mitochondria also activated the quiescent MCC of mouse mitoplasts and induced flickering of active MCC reconstituted from yeast mitochondrial membranes. Moreover, relative peptide efficacies were very similar for mitochondrial swelling and both types of patch-clamp experiments. We propose that patch-clamp recordings of MCC activity and the high-amplitude swelling induced by signal peptides reflect the opening of a single channel. Based on the selective responsiveness of that channel to signal peptides and the dependence of its opening in isolated mitochondria on membrane potential, we further suggest that the channel is involved in the mitochondrial protein import process.

AB - We have reported that the signal presequence of cytochrome oxidase subunit IV from Neurospora crassa increases the permeability of isolated rat liver mitochondria [P. M. Sokolove and K. W. Kinnally (1996) Arch. Biochem. Biophys. 336, 69] and regulates the behavior of the mutiple conductance channel (MCC) of yeast inner mitochondrial membrane [T. A. Lohret and K. W. Kinnally (1995) J. Biol. Chem. 270, 15950]. Here we examine in greater detail the action of a number of mitochondrial presequences from various sources and of several control peptides on the permeability of isolated rat liver mitochondria and on MCC activity monitored via patch-clamp techniques in both mammalian mitoplasts and a reconstituted yeast system. The data indicate that the ability to alter mitochondrial permeability is a property of most, but not all, signal peptides. Furthermore, it is clear that, although signal peptides are characterized by positive charge and the ability to form amphiphilic α helices, these two characteristics are not sufficient to guarantee mitochondrial effects. Finally, the results reveal a strong correlation between peptide effects on the permeability of isolated mitochondria and on MCC activity: peptides that induced swelling of mouse and rat mitochondria also activated the quiescent MCC of mouse mitoplasts and induced flickering of active MCC reconstituted from yeast mitochondrial membranes. Moreover, relative peptide efficacies were very similar for mitochondrial swelling and both types of patch-clamp experiments. We propose that patch-clamp recordings of MCC activity and the high-amplitude swelling induced by signal peptides reflect the opening of a single channel. Based on the selective responsiveness of that channel to signal peptides and the dependence of its opening in isolated mitochondria on membrane potential, we further suggest that the channel is involved in the mitochondrial protein import process.

KW - Mitochondria

KW - Multiple conductance channel

KW - Permeability transition

KW - Protein import

KW - Signal peptides

UR - http://www.scopus.com/inward/record.url?scp=0033150885&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033150885&partnerID=8YFLogxK

U2 - 10.1006/abbi.1999.1190

DO - 10.1006/abbi.1999.1190

M3 - Article

VL - 366

SP - 107

EP - 115

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 1

ER -