Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase

Andrea Carrer, Ludovica Tommasin, Justina Šileikytė, Francesco Ciscato, Riccardo Filadi, Andrea Urbani, Michael Forte, Andrea Rasola, Ildikò Szabò, Michela Carraro () and Paolo Bernardi ()
Additional contact information
Andrea Carrer: University of Padova
Ludovica Tommasin: University of Padova
Justina Šileikytė: Vollum Institute, Oregon Health and Science University
Francesco Ciscato: University of Padova
Riccardo Filadi: University of Padova
Andrea Urbani: University of Padova
Michael Forte: Vollum Institute, Oregon Health and Science University
Andrea Rasola: University of Padova
Ildikò Szabò: Consiglio Nazionale delle Ricerche Neuroscience Institute
Michela Carraro: University of Padova
Paolo Bernardi: University of Padova

Nature Communications, 2021, vol. 12, issue 1, 1-12

Abstract: Abstract F-ATP synthase is a leading candidate as the mitochondrial permeability transition pore (PTP) but the mechanism(s) leading to channel formation remain undefined. Here, to shed light on the structural requirements for PTP formation, we test cells ablated for g, OSCP and b subunits, and ρ0 cells lacking subunits a and A6L. Δg cells (that also lack subunit e) do not show PTP channel opening in intact cells or patch-clamped mitoplasts unless atractylate is added. Δb and ΔOSCP cells display currents insensitive to cyclosporin A but inhibited by bongkrekate, suggesting that the adenine nucleotide translocator (ANT) can contribute to channel formation in the absence of an assembled F-ATP synthase. Mitoplasts from ρ0 mitochondria display PTP currents indistinguishable from their wild-type counterparts. In this work, we show that peripheral stalk subunits are essential to turn the F-ATP synthase into the PTP and that the ANT provides mitochondria with a distinct permeability pathway.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25161-x Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25161-x

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25161-x

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().