bims-resufa 2019-12-29 papers

Issue of 2019–12–29
two papers selected by
Vera Strogolova, Marquette University

Sci Rep. 2019 Dec 27. 9(1): 20207

Proton-transfer pathways in the mitochondrial S. cerevisiae cytochrome c oxidase.

Markus L Björck, Jóhanna Vilhjálmsdóttir, Andrew M Hartley, Brigitte Meunier, Linda Näsvik Öjemyr, Amandine Maréchal, Peter Brzezinski.

In cytochrome c oxidase (CytcO) reduction of O2 to water is linked to uptake of eight protons from the negative side of the membrane: four are substrate protons used to form water and four are pumped across the membrane. In bacterial oxidases, the substrate protons are taken up through the K and the D proton pathways, while the pumped protons are transferred through the D pathway. On the basis of studies with CytcO isolated from bovine heart mitochondria, it was suggested that in mitochondrial CytcOs the pumped protons are transferred though a third proton pathway, the H pathway, rather than through the D pathway. Here, we studied these reactions in S. cerevisiae CytcO, which serves as a model of the mammalian counterpart. We analyzed the effect of mutations in the D (Asn99Asp and Ile67Asn) and H pathways (Ser382Ala and Ser458Ala) and investigated the kinetics of electron and proton transfer during the reaction of the reduced CytcO with O2. No effects were observed with the H pathway variants while in the D pathway variants the functional effects were similar to those observed with the R. sphaeroides CytcO. The data indicate that the S. cerevisiae CytcO uses the D pathway for proton uptake and presumably also for proton pumping.

DOI: https://doi.org/10.1038/s41598-019-56648-9

Mitochondrion. 2019 Dec 20. pii: S1567-7249(19)30143-6. [Epub ahead of print]

OPA1 regulates respiratory supercomplexes assembly: the role of mitochondrial swelling.

Sehwan Jang, Sabzali Javadov.

Optic atrophy type 1 protein (OPA1), a dynamin-related GTPase, that, in addition to mitochondrial fusion, plays an important role in maintaining the structural organization and integrity of the inner mitochondrial membrane (IMM). OPA1 exists in two forms: IMM-bound long-OPA1 (L-OPA1) and soluble short-OPA1 (S-OPA1), a product of L-OPA1 proteolytic cleavage localized in the intermembrane space. In addition to OPA1, the structural and functional integrity of IMM can be regulated by changes in the matrix volume due to the opening/closure of permeability transition pores (PTP). Herein, we investigated the crosstalk between the PTP and OPA1 to clarify whether PTP opening is involved in OPA1-mediated regulation of respiratory chain supercomplexes (RCS) assembly using cardiac mitochondria and cell line. We found that: 1) Proteolytic cleavage of L-OPA1 is stimulated by PTP-induced mitochondrial swelling, 2) OPA1 knockdown reduces PTP-induced mitochondrial swelling but enhances ROS production, 3) OPA1 deficiency impairs the RCS assembly associated with diminished ETC activity and oxidative phosphorylation, 4) OPA1 has no physical interaction with phospholipid scramblase 3 although OPA1 downregulation increases expression of the scramblase. Thus, this study demonstrates that L-OPA1 cleavage depends on the PTP-induced mitochondrial swelling suggesting a regulatory role of the PTP-OPA1 axis in RCS assembly and mitochondrial bioenergetics.

Keywords: mitochondria; mitochondrial swelling; optic atrophy type 1 protein; permeability transition pore; respiratory supercomplexes

DOI: https://doi.org/10.1016/j.mito.2019.11.006