Pharaoh 2023 Geroscience

From Bioblast
Publications in the MiPMap
Pharaoh G, Kamat V, Kannan S, Stuppard RS, Whitson J, MartΓ­n-PΓ©rez M, Qian WJ, MacCoss MJ, VillΓ©n J, Rabinovitch P, Campbell MD, Sweet IR, Marcinek DJ (2023) The mitochondrially targeted peptide elamipretide (SS-31) improves ADP sensitivity in aged mitochondria by increasing uptake through the adenine nucleotide translocator (ANT).

Β» Geroscience [Epub ahead of print]. PMID: 37462785 Open Access

Pharaoh Gavin, Kamat Varun, Kannan Sricharan, Stuppard Rudolph S, Whitson Jeremy, Martin-Perez Miguel, Qian Wei-Jun, MacCoss Michael J, Villen Judit, Rabinovitch Peter, Campbell Matthew D, Sweet Ian R, Marcinek David J (2023) Geroscience

Abstract: Aging muscle experiences functional decline in part mediated by impaired mitochondrial ADP sensitivity. Elamipretide (ELAM) rapidly improves physiological and mitochondrial function in aging and binds directly to the mitochondrial ADP transporter ANT. We hypothesized that ELAM improves ADP sensitivity in aging leading to rescued physiological function. We measured the response to ADP stimulation in young and old muscle mitochondria with ELAM treatment, in vivo heart and muscle function, and compared protein abundance, phosphorylation, and S-glutathionylation of ADP/ATP pathway proteins. ELAM treatment increased ADP sensitivity in old muscle mitochondria by increasing uptake of ADP through the ANT and rescued muscle force and heart systolic function. Protein abundance in the ADP/ATP transport and synthesis pathway was unchanged, but ELAM treatment decreased protein s-glutathionylation incuding of ANT. Mitochondrial ADP sensitivity is rapidly modifiable. This research supports the hypothesis that ELAM improves ANT function in aging and links mitochondrial ADP sensitivity to physiological function. ELAM binds directly to ANT and ATP synthase and ELAM treatment improves ADP sensitivity, increases ATP production, and improves physiological function in old muscles. β€’ Keywords: ATP production, Adenine nucleotide translocator (ANT), Adenosine diphosphate (ADP) sensitivity, Elamipretide or SS-31, Mitochondrial dysfunction, Oxygen consumption rate (OCR) β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: US OK Oklahoma City Van Remmen H, US WA Seattle Marcinek DJ

Pharaoh 2023 Geroscience CORRECTION.png

Correction: FADH2 and Complex II

Ambiguity alert.png
FADH2 is shown as the substrate feeding electrons into Complex II (CII). This is wrong and requires correction - for details see Gnaiger (2024).
Gnaiger E (2024) Complex II ambiguities ― FADH2 in the electron transfer system. J Biol Chem 300:105470. - Β»Bioblast linkΒ«

Labels: MiParea: Respiration, Pharmacology;toxicology  Pathology: Aging;senescence 

Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue, Isolated mitochondria 

Regulation: ADP  Coupling state: LEAK, OXPHOS  Pathway: N, S, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer 

2023-07, AmR 

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