Insulin enhances mitochondrial inner membrane potential and increases ATP levels through phosphoinositide 3-kinase in adult sensory neurons

2005 ◽  
Vol 28 (1) ◽  
pp. 42-54 ◽  
Author(s):  
Tze-Jen Huang ◽  
Alex Verkhratsky ◽  
Paul Fernyhough
Keyword(s):  
Membrane Potential ◽  
Sensory Neurons ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Atp Levels ◽  
Phosphoinositide 3 Kinase

Abstract 332: Mitochondrial Inner-Membrane Potential Instability Promotes Sarcolemmal Electrical Instability after Ischemia-Reperfusion in Monolayers of Cardiac Myocytes

2013 ◽  
Vol 113 (suppl_1) ◽  
Author(s):  
Soroosh Solhjoo ◽  
Brian O’Rourke
Keyword(s):  
Membrane Potential ◽  
Cardiac Myocytes ◽  
Mitochondrial Function ◽  
Ischemia Reperfusion ◽  
Neonatal Rat ◽  
Partial Recovery ◽  
Mitochondrial Network ◽  
Electrical Excitability ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

Mitochondrial uncoupling due to oxidative stress can, through opening of sarcolemmal KATP channels, alter cellular electrical excitability, and it has been proposed that mitochondrial function is a major factor in arrhythmogenesis during ischemia-reperfusion. Here, we examine the effects of ischemia-reperfusion on mitochondrial inner membrane potential (ΔΨm) and corresponding changes in electrical excitability and wave propagation in monolayer cultures of neonatal rat ventricular myocytes. Changes in ΔΨm were observed using TMRM and changes in the sarcolemmal voltage were recorded with a 464-element photodiode array using di-4-ANEPPS. Ischemia was induced by covering the center part of the monolayer (D = 22 mm) with a coverslip (D = 15 mm). Cell contractions ceased after approximately 6 min of ischemia; however, electrical activity continued for 11.3 ± 4.2 min (N = 5). Amplitude and conduction velocity of the action potentials in the ischemic region decreased over the same time period. ΔΨm was lost in two phases: a reversible phase of partial depolarization, after 11.2 ± 1.3 min of ischemia, and a nonreversible phase, which happened after 30 ± 6 min of ischemia, during which the whole mitochondrial network of the myocyte became depolarized and the cells underwent contracture (N = 4). Reperfusion after the long ischemia resulted in only partial recovery and the observance of oscillations of ΔΨm in the mitochondrial network or rapid flickering of individual mitochondrial clusters and was associated with heterogeneous electrical recovery, and formation of wavelets and reentry (4/5 monolayers). In contrast, mitochondria fully recovered and reentry was rare (1/5 monolayers) for reperfusion after the short ischemia (10-12 min). 4’-chlorodiazepam, an inhibitor of inner membrane anion channels, stabilized mitochondrial function after the long ischemia, and prevented wavelets (5/5 monolayers) and reentry (4/5 monolayers). In conclusion, incomplete or unstable recovery of mitochondrial function after ischemia correlates with reentrant arrhythmias in monolayers of cardiac myocytes. Our findings suggest that stabilization of mitochondrial network dynamics is an important strategy for preventing ischemia/reperfusion-related arrhythmias.

scholarly journals Insulin Prevents Depolarization of the Mitochondrial Inner Membrane in Sensory Neurons of Type 1 Diabetic Rats in the Presence of Sustained Hyperglycemia

Diabetes ◽  
2003 ◽  
Vol 52 (8) ◽  
pp. 2129-2136 ◽  
Author(s):  
T.-J. Huang ◽  
S. A. Price ◽  
L. Chilton ◽  
N. A. Calcutt ◽  
D. R. Tomlinson ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Diabetic Rats ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

scholarly journals The translocator maintenance protein Tam41 is required for mitochondrial cardiolipin biosynthesis

2008 ◽  
Vol 183 (7) ◽  
pp. 1213-1221 ◽  
Author(s):  
Stephan Kutik ◽  
Michael Rissler ◽  
Xue Li Guan ◽  
Bernard Guiard ◽  
Guanghou Shui ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Respiratory Chain ◽  
Matrix Protein ◽  
Mitochondrial Protein ◽  
Pleiotropic Effects ◽  
Mitochondrial Matrix ◽  
Carrier Proteins ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane

The mitochondrial inner membrane contains different translocator systems for the import of presequence-carrying proteins and carrier proteins. The translocator assembly and maintenance protein 41 (Tam41/mitochondrial matrix protein 37) was identified as a new member of the mitochondrial protein translocator systems by its role in maintaining the integrity and activity of the presequence translocase of the inner membrane (TIM23 complex). Here we demonstrate that the assembly of proteins imported by the carrier translocase, TIM22 complex, is even more strongly affected by the lack of Tam41. Moreover, respiratory chain supercomplexes and the inner membrane potential are impaired by lack of Tam41. The phenotype of Tam41-deficient mitochondria thus resembles that of mitochondria lacking cardiolipin. Indeed, we found that Tam41 is required for the biosynthesis of the dimeric phospholipid cardiolipin. The pleiotropic effects of the translocator maintenance protein on preprotein import and respiratory chain can be attributed to its role in biosynthesis of mitochondrial cardiolipin.

scholarly journals Yeast mitochondria lacking the phosphate carrier/p32 are blocked in phosphate transport but can import preproteins after regeneration of a membrane potential.

1996 ◽  
Vol 16 (11) ◽  
pp. 6524-6531 ◽  
Author(s):  
V Zara ◽  
K Dietmeier ◽  
A Palmisano ◽  
A Vozza ◽  
J Rassow ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Outer Membrane ◽  
Protein Import ◽  
Outer Membrane Proteins ◽  
Phosphate Transport ◽  
Inner Membrane ◽  
Saccharomyces Cerevisiae Mitochondria ◽  
Mitochondrial Inner Membrane ◽  
Precursor Proteins ◽  
Phosphate Carrier

Two different functions have been proposed for the phosphate carrier protein/p32 of Saccharomyces cerevisiae mitochondria: transport of phosphate and requirement for import of precursor proteins into mitochondria. We characterized a yeast mutant lacking the gene for the phosphate carrier/p32 and found both a block in the import of phosphate and a strong reduction in the import of preproteins transported to the mitochondrial inner membrane and matrix. Binding of preproteins to the surface of mutant mitochondria and import of outer membrane proteins were not inhibited, indicating that the inhibition of protein import occurred after the recognition step at the outer membrane. The membrane potential across the inner membrane of the mutant mitochondria was strongly reduced. Restoration of the membrane potential restored preprotein import but did not affect the block of phosphate transport of the mutant mitochondria. We conclude that the inhibition of protein import into mitochondria lacking the phosphate carrier/p32 is indirectly caused by a reduction of the mitochondrial membrane potential (delta(gamma)), and we propose a model that the reduction of delta(psi) is due to the defective phosphate import, suggesting that phosphate transport is the primary function of the phosphate carrier/p32.

scholarly journals Suppression of Mitochondrial DNA Instability of Autosomal Dominant Forms of Progressive External Ophthalmoplegia-Associated ANT1 Mutations in Podospora anserina

Genetics ◽  
2009 ◽  
Vol 183 (3) ◽  
pp. 861-871 ◽  
Author(s):  
Riyad El-Khoury ◽  
Annie Sainsard-Chanet
Keyword(s):  
Mitochondrial Dna ◽  
Membrane Potential ◽  
Large Scale ◽  
Autosomal Dominant ◽  
Adenine Nucleotide ◽  
Podospora Anserina ◽  
Progressive External Ophthalmoplegia ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
Mtdna Deletions

Maintenance and expression of mitochondrial DNA (mtDNA) are essential for the cell and the organism. In humans, several mutations in the adenine nucleotide translocase gene ANT1 are associated with multiple mtDNA deletions and autosomal dominant forms of progressive external ophthalmoplegia (adPEO). The mechanisms underlying the mtDNA instability are still obscure. A current hypothesis proposes that these pathogenic mutations primarily uncouple the mitochondrial inner membrane, which secondarily causes mtDNA instability. Here we show that the three adPEO-associated mutations equivalent to A114P, L98P, and V289M introduced into the Podospora anserina ANT1 ortholog dominantly cause severe growth defects, decreased reactive oxygen species production (ROS), decreased mitochondrial inner membrane potential (Δψ), and accumulation of large-scale mtDNA deletions leading to premature death. Interestingly, we show that, at least for the adPEO-type M106P and A121P mutant alleles, the associated mtDNA instability cannot be attributed only to a reduced membrane potential or to an increased ROS level since it can be suppressed without restoration of the Δψ or modification of the ROS production. Suppression of mtDNA instability due to the M106P and A121P mutations was obtained by an allele of the rmp1 gene involved in nucleo-mitochondrial cross- talk and also by an allele of the AS1 gene encoding a cytosolic ribosomal protein. In contrast, the mtDNA instability caused by the S296M mutation was not suppressed by these alleles.

Differential effects of linoleic and alpha-linolenic fatty acids on spatial and temporal mitochondrial distribution and activity in bovine oocytes

2012 ◽  
Vol 24 (5) ◽  
pp. 679 ◽  
Author(s):  
Waleed F. Marei ◽  
D. Claire Wathes ◽  
Ali A. Fouladi-Nashta
Keyword(s):  
Membrane Potential ◽  
Oocyte Maturation ◽  
Inhibitory Effect ◽  
Inner Membrane ◽  
Nuclear Maturation ◽  
Mitochondrial Inner Membrane ◽  
Maturation Rate ◽  
Microscope Imaging ◽  
Mitochondrial Distribution ◽  
Bovine Oocytes

Using specific stains and confocal microscope imaging, the patterns of mitochondrial distribution, mitochondrial inner membrane potential and reactive oxygen species (ROS) levels during bovine oocyte maturation were determined in the presence or absence of physiological concentrations of linoleic acid (LA; 100 µM) or α-linolenic acid (ALA; 50 µM). Mitochondrial distribution in control oocytes at 0 h was mainly peripheral and changed to a diffused pattern after 1 h of culture; this was maintained up to 24 h. Mitochondrial clusters were observed during the early hours of maturation (1–4 h); the majority of these were arranged in perinuclear fashion. LA supplementation resulted in: (1) delayed redistribution of the mitochondria from a peripheral to a diffuse pattern and a decreased percentages of oocytes showing perinuclear mitochondrial clusters, (2) decreased mitochondrial inner membrane potential at 1 and 24 h compared with the control and (3) higher ROS levels, associated with a lower nuclear maturation rate. In contrast, ALA supplementation had no effect on mitochondrial distribution and activity and decreased ROS levels compared with the control; this was associated with an increased nuclear maturation rate. In conclusion, LA induced alterations in mitochondrial distribution and activity as well as increasing ROS levels, which mediate, at least in part, the inhibitory effect on oocyte maturation.

scholarly journals Membrane Potential-Driven Protein Import into Mitochondria

2000 ◽  
Vol 11 (11) ◽  
pp. 3977-3991 ◽  
Author(s):  
Andreas Geissler ◽  
Thomas Krimmer ◽  
Ulf Bömer ◽  
Bernard Guiard ◽  
Joachim Rassow ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Protein Import ◽  
Driving Mechanism ◽  
Unexpected Finding ◽  
Inner Membrane ◽  
Mitochondrial Inner Membrane ◽  
The Matrix ◽  
Mitochondrial Hsp70 ◽  
A Charge ◽  
Electrophoretic Effect

The transport of preproteins into or across the mitochondrial inner membrane requires the membrane potential Δψ across this membrane. Two roles of Δψ in the import of cleavable preproteins have been described: an electrophoretic effect on the positively charged matrix-targeting sequences and the activation of the translocase subunit Tim23. We report the unexpected finding that deletion of a segment within the sorting sequence of cytochromeb 2 , which is located behind the matrix-targeting sequence, strongly influenced the Δψ-dependence of import. The differential Δψ-dependence was independent of the submitochondrial destination of the preprotein and was not attributable to the requirement for mitochondrial Hsp70 or Tim23. With a series of preprotein constructs, the net charge of the sorting sequence was altered, but the Δψ-dependence of import was not affected. These results suggested that the sorting sequence contributed to the import driving mechanism in a manner distinct from the two known roles of Δψ. Indeed, a charge-neutral amino acid exchange in the hydrophobic segment of the sorting sequence generated a preprotein with an even better import, i.e. one with lower Δψ-dependence than the wild-type preprotein. The sorting sequence functioned early in the import pathway since it strongly influenced the efficiency of translocation of the matrix-targeting sequence across the inner membrane. These results suggest a model whereby an electrophoretic effect of Δψ on the matrix-targeting sequence is complemented by an import-stimulating activity of the sorting sequence.

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