A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+

Dubinin, Mikhail V.; Самарцев, В. Н.; Astashev, Maxim E.; Kazakov, Alexei S.; Belosludtsev, Konstantin N.

doi:10.1007/s00249-014-0986-5

Cited by 7 publications

(1 citation statement)

References 34 publications

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“…The bidirectional movement of lipids between the ER and mitochondria may be mediated by interactions between MAM and mitochondria (Vance, 2014). Literature regarding HA clearly suggests a role in mitochondrial membrane permeability (Dubinin et al, 2013;Dubinin et al, 2014a;Dubinin et al, 2014b;Vedernikov et al, 2015). This aspect opens up potential new lines of research with respect to GDAP1, HA, and mitochondrial metabolism and permeability.…”

Section: Functional Considerationsmentioning

confidence: 96%

Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations

Nguyen

Sutinen

Raasakka

et al. 2021

Front. Mol. Biosci.

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Charcot-Marie-Tooth disease (CMT) is one of the most common inherited neurological disorders. Despite the common involvement of ganglioside-induced differentiation-associated protein 1 (GDAP1) in CMT, the protein structure and function, as well as the pathogenic mechanisms, remain unclear. We determined the crystal structure of the complete human GDAP1 core domain, which shows a novel mode of dimerization within the glutathione S-transferase (GST) family. The long GDAP1-specific insertion forms an extended helix and a flexible loop. GDAP1 is catalytically inactive toward classical GST substrates. Through metabolite screening, we identified a ligand for GDAP1, the fatty acid hexadecanedioic acid, which is relevant for mitochondrial membrane permeability and Ca2+ homeostasis. The fatty acid binds to a pocket next to a CMT-linked residue cluster, increases protein stability, and induces changes in protein conformation and oligomerization. The closest homologue of GDAP1, GDAP1L1, is monomeric in its full-length form. Our results highlight the uniqueness of GDAP1 within the GST family and point toward allosteric mechanisms in regulating GDAP1 oligomeric state and function.

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Section: Functional Considerationsmentioning

confidence: 96%

Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations

Nguyen

Sutinen

Raasakka

et al. 2021

Front. Mol. Biosci.

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Ca2+-dependent nonspecific permeability of the inner membrane of liver mitochondria in the guinea fowl (Numida meleagris)

Vedernikov

Dubinin

Zabiakin

et al. 2015

J Bioenerg Biomembr

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This comparative study presents the results of the induction of Ca(2+)-dependent nonspecific permeability of the inner membrane (pore opening) of rat and guinea fowl liver mitochondria by mechanisms that are both sensitive and insensitive to cyclosporin A (CsA). It was established that energized rat and guinea fowl liver mitochondria incubated with 1 mM of inorganic phosphate (Pi) are capable of swelling upon addition of at least 125 and 875 nmol of CaCl2 per 1 mg protein, respectively. Under these conditions, the Ca(2+) release from the mitochondria of these animals and a drop in Δψ are observed. All of these processes are inhibited by 1 μM of CsA. FCCP, causing organelle de-energization, induces pore opening in rat and guinea fowl liver mitochondria upon addition of 45 и 625 nmol of CaCl2 per 1 mg protein, respectively. These results suggest the existence of a CsA-sensitive mechanism for the induction of Ca(2+)-dependent pores in guinea fowl liver mitochondria, which has been reported in rat liver mitochondria. However, guinea fowl liver mitochondria have a significantly greater resistance to Ca(2+) as a pore inducer compared to rat liver mitochondria. It was found that the addition of α,ω-hexadecanedioic acid (HDA) to rat and guinea fowl liver mitochondria incubated with CsA and loaded with Ca(2+) causes organelle swelling and Ca(2+) release from the matrix. It is assumed that in contrast to the CsA-sensitive pore, the CsA-insensitive pore induced by HDA in the inner membrane of guinea fowl liver mitochondria, as well as in rat liver mitochondria, is lipid in nature.

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Membranotropic effects of ω-hydroxypalmitic acid and Ca2+ on rat liver mitochondria and lecithin liposomes. Aggregation and membrane permeabilization

Dubinin

Самарцев

Stepanova

et al. 2018

J Bioenerg Biomembr

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The paper examines membranotropic Ca-dependent effects of ω-hydroxypalmitic acid (HPA), a product of ω-oxidation of fatty acids, on the isolated rat liver mitochondria and artificial membrane systems (liposomes). It was established that in the presence of Ca, HPA induced aggregation of liver mitochondria, which was accompanied by the release of cytochrome c from the organelles. It was further demonstrated that the addition of Ca to HPA-containing liposomes induced their aggregation and/or fusion. Ca also caused the release of the fluorescent dye sulforhodamine B from liposomes, indicating their permeabilization. HPA was shown to induce a high-amplitude swelling of Ca-loaded mitochondria, to decrease their membrane potential, to induce the release of Ca from the organelles and to result in the oxidation of the mitochondrial NAD(P)H pool. Those effects of HPA were not blocked by the MPT pore inhibitor CsA, but were suppressed by the mitochondrial calcium uniporter inhibitor ruthenium red. The effects of HPA were also observed when Ca was replaced with Sr (but not with Ba or Mg). A supposition is made that HPA can induce a Ca-dependent aggregation of mitochondria, as well as Cadependent CsA-insensitive permeabilization of the inner mitochondrial membrane - with the subsequent lysis of the organelles.

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A permeability transition in liver mitochondria and liposomes induced by α,ω-dioic acids and Ca2+

Cited by 7 publications

References 34 publications

Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations

Structure of the Complete Dimeric Human GDAP1 Core Domain Provides Insights into Ligand Binding and Clustering of Disease Mutations

Ca2+-dependent nonspecific permeability of the inner membrane of liver mitochondria in the guinea fowl (Numida meleagris)

Membranotropic effects of ω-hydroxypalmitic acid and Ca2+ on rat liver mitochondria and lecithin liposomes. Aggregation and membrane permeabilization

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