Limits...
Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption.

Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R - J. Cell. Mol. Med. (2012)

Bottom Line: Lack or inhibition of mitochondrial Cx43 is associated with reduced mitochondrial potassium influx, which might affect mitochondrial respiration.Acute inhibition of Cx43 in rat left ventricular (LV) SSM by 18α glycyrrhetinic acid (GA) or Cx43 mimetic peptides (Cx43-MP) reduced ADP-stimulated complex I respiration and ATP generation.Taken together, mitochondrial Cx43 is required for optimal complex I activity and respiration and thus mitochondrial ATP-production.

View Article: PubMed Central - PubMed

Affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Essen, Germany.

Show MeSH
Effect of connexin mimetic peptides on mitochondrial oxygen consumption and ATP production. (A) Basal and ADP-stimulated respiration using substrates for complex I or complex II, respectively, were measured in untreated rat LV SSM (n = 12), or SSM incubated with 250 μmol/l Cx40- (n = 12) or Cx43-MP (n = 12), respectively. *P < 0.05 versus untreated, #P < 0.05 versus Cx40-MP. (B) Original traces demonstrating luciferase activities of isolated rat SSM before and after addition of 500 μmol/l ADP under control conditions (untreated) and with Cx43 inhibition by 250 μmol/l Cx43-MP. Oligomycin, which inhibits the ATP synthase, was used as negative control. (C) ATP generation was quantified as the area under the curve for the first minute after addition of ADP in untreated or Cx43-MP-treated rat SSM (n = 15), *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3822677&req=5

fig02: Effect of connexin mimetic peptides on mitochondrial oxygen consumption and ATP production. (A) Basal and ADP-stimulated respiration using substrates for complex I or complex II, respectively, were measured in untreated rat LV SSM (n = 12), or SSM incubated with 250 μmol/l Cx40- (n = 12) or Cx43-MP (n = 12), respectively. *P < 0.05 versus untreated, #P < 0.05 versus Cx40-MP. (B) Original traces demonstrating luciferase activities of isolated rat SSM before and after addition of 500 μmol/l ADP under control conditions (untreated) and with Cx43 inhibition by 250 μmol/l Cx43-MP. Oligomycin, which inhibits the ATP synthase, was used as negative control. (C) ATP generation was quantified as the area under the curve for the first minute after addition of ADP in untreated or Cx43-MP-treated rat SSM (n = 15), *P < 0.05.

Mentions: Rat LV SSM were incubated with Cx43-mimetic peptides (Cx43-MP), which are known to block Cx43-hemichannels [14]. Cx43-MP reduced ADP-stimulated complex I, but not complex II respiration, compared with control Cx40-MP peptides (Fig. 2A). Basal respiration was similar between groups. Cx43-MP did not reduce ADP-stimulated complex I respiration in IFM, which do not contain Cx43 compared with Cx40-MP (in nmol O2/mg*min., basal respiration: untreated: 17.0 ± 2.0; Cx40-MP: 19.3 ± 1.7; Cx43-MP: 20.3 ± 1.7; ADP-stimulated respiration: untreated: 74.9 ± 6.1; Cx40-MP: 58.1 ± 4.5; Cx43-MP: 58.6 ± 4.8, n = 8, P = ns Cx40-MP versus Cx43-MP). To exclude unspecific effects of Cx43-MP, ADP-stimulated complex I respiration was measured in LV SSM from conditional Cx43-knockout mice. Here, Cx43-MP also had no effect on ADP-stimulated complex I respiration (Cx43fl/fl: 34.2 ± 2.4 nmol O2/mg*min., n = 8 versus Cx43Cre-ER(T)/fl + 4-OHT: 33.5 ± 1.9 nmol O2/mg*min., n = 14, P = ns).


Mitochondrial connexin 43 impacts on respiratory complex I activity and mitochondrial oxygen consumption.

Boengler K, Ruiz-Meana M, Gent S, Ungefug E, Soetkamp D, Miro-Casas E, Cabestrero A, Fernandez-Sanz C, Semenzato M, Di Lisa F, Rohrbach S, Garcia-Dorado D, Heusch G, Schulz R - J. Cell. Mol. Med. (2012)

Effect of connexin mimetic peptides on mitochondrial oxygen consumption and ATP production. (A) Basal and ADP-stimulated respiration using substrates for complex I or complex II, respectively, were measured in untreated rat LV SSM (n = 12), or SSM incubated with 250 μmol/l Cx40- (n = 12) or Cx43-MP (n = 12), respectively. *P < 0.05 versus untreated, #P < 0.05 versus Cx40-MP. (B) Original traces demonstrating luciferase activities of isolated rat SSM before and after addition of 500 μmol/l ADP under control conditions (untreated) and with Cx43 inhibition by 250 μmol/l Cx43-MP. Oligomycin, which inhibits the ATP synthase, was used as negative control. (C) ATP generation was quantified as the area under the curve for the first minute after addition of ADP in untreated or Cx43-MP-treated rat SSM (n = 15), *P < 0.05.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3822677&req=5

fig02: Effect of connexin mimetic peptides on mitochondrial oxygen consumption and ATP production. (A) Basal and ADP-stimulated respiration using substrates for complex I or complex II, respectively, were measured in untreated rat LV SSM (n = 12), or SSM incubated with 250 μmol/l Cx40- (n = 12) or Cx43-MP (n = 12), respectively. *P < 0.05 versus untreated, #P < 0.05 versus Cx40-MP. (B) Original traces demonstrating luciferase activities of isolated rat SSM before and after addition of 500 μmol/l ADP under control conditions (untreated) and with Cx43 inhibition by 250 μmol/l Cx43-MP. Oligomycin, which inhibits the ATP synthase, was used as negative control. (C) ATP generation was quantified as the area under the curve for the first minute after addition of ADP in untreated or Cx43-MP-treated rat SSM (n = 15), *P < 0.05.
Mentions: Rat LV SSM were incubated with Cx43-mimetic peptides (Cx43-MP), which are known to block Cx43-hemichannels [14]. Cx43-MP reduced ADP-stimulated complex I, but not complex II respiration, compared with control Cx40-MP peptides (Fig. 2A). Basal respiration was similar between groups. Cx43-MP did not reduce ADP-stimulated complex I respiration in IFM, which do not contain Cx43 compared with Cx40-MP (in nmol O2/mg*min., basal respiration: untreated: 17.0 ± 2.0; Cx40-MP: 19.3 ± 1.7; Cx43-MP: 20.3 ± 1.7; ADP-stimulated respiration: untreated: 74.9 ± 6.1; Cx40-MP: 58.1 ± 4.5; Cx43-MP: 58.6 ± 4.8, n = 8, P = ns Cx40-MP versus Cx43-MP). To exclude unspecific effects of Cx43-MP, ADP-stimulated complex I respiration was measured in LV SSM from conditional Cx43-knockout mice. Here, Cx43-MP also had no effect on ADP-stimulated complex I respiration (Cx43fl/fl: 34.2 ± 2.4 nmol O2/mg*min., n = 8 versus Cx43Cre-ER(T)/fl + 4-OHT: 33.5 ± 1.9 nmol O2/mg*min., n = 14, P = ns).

Bottom Line: Lack or inhibition of mitochondrial Cx43 is associated with reduced mitochondrial potassium influx, which might affect mitochondrial respiration.Acute inhibition of Cx43 in rat left ventricular (LV) SSM by 18α glycyrrhetinic acid (GA) or Cx43 mimetic peptides (Cx43-MP) reduced ADP-stimulated complex I respiration and ATP generation.Taken together, mitochondrial Cx43 is required for optimal complex I activity and respiration and thus mitochondrial ATP-production.

View Article: PubMed Central - PubMed

Affiliation: Institut für Pathophysiologie, Universitätsklinikum Essen, Essen, Germany.

Show MeSH