Identification of an ATP-sensitive potassium channel in mitochondria

Angela Paggio, Vanessa Checchetto, Antonio Campo, Roberta Menabò, Giulia Marco, Fabio Lisa, Ildiko Szabo, Rosario Rizzuto () and Diego De Stefani ()
Additional contact information
Angela Paggio: University of Padova
Vanessa Checchetto: University of Padova
Antonio Campo: University of Padova
Roberta Menabò: CNR Institute of Neuroscience
Giulia Marco: University of Padova
Fabio Lisa: University of Padova
Ildiko Szabo: University of Padova
Rosario Rizzuto: University of Padova
Diego De Stefani: University of Padova

Nature, 2019, vol. 572, issue 7771, 609-613

Abstract: Abstract Mitochondria provide chemical energy for endoergonic reactions in the form of ATP, and their activity must meet cellular energy requirements, but the mechanisms that link organelle performance to ATP levels are poorly understood. Here we confirm the existence of a protein complex localized in mitochondria that mediates ATP-dependent potassium currents (that is, mitoKATP). We show that—similar to their plasma membrane counterparts—mitoKATP channels are composed of pore-forming and ATP-binding subunits, which we term MITOK and MITOSUR, respectively. In vitro reconstitution of MITOK together with MITOSUR recapitulates the main properties of mitoKATP. Overexpression of MITOK triggers marked organelle swelling, whereas the genetic ablation of this subunit causes instability in the mitochondrial membrane potential, widening of the intracristal space and decreased oxidative phosphorylation. In a mouse model, the loss of MITOK suppresses the cardioprotection that is elicited by pharmacological preconditioning induced by diazoxide. Our results indicate that mitoKATP channels respond to the cellular energetic status by regulating organelle volume and function, and thereby have a key role in mitochondrial physiology and potential effects on several pathological processes.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41586-019-1498-3 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

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:nature:v:572:y:2019:i:7771:d:10.1038_s41586-019-1498-3

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

DOI: 10.1038/s41586-019-1498-3

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

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