Styles 2021 Cell Death Dis
|Styles FL, Al-Owais MM, Scragg JL, Chuntharpursat-Bon E, Hettiarachchi NT, Lippiat JD, Minard A, Bon RS, Porter K, Sukumar P, Peers C, Roberts LD (2021) Kv1.3 voltage-gated potassium channels link cellular respiration to proliferation through a non-conducting mechanism. Cell Death Dis 12:372.|
Styles Faye L, Al-Owais Moza M, Scragg Jason L, Chuntharpursat-Bon Eulashini, Hettiarachchi Nishani T, Lippiat Jonathan D, Minard Aisling, Bon Robin S, Porter Karen, Sukumar Piruthivi, Peers Chris, Roberts Lee D (2021) Cell Death Dis
Abstract: Cellular energy metabolism is fundamental for all biological functions. Cellular proliferation requires extensive metabolic reprogramming and has a high energy demand. The Kv1.3 voltage-gated potassium channel drives cellular proliferation. Kv1.3 channels localise to mitochondria. Using high-resolution respirometry, we show Kv1.3 channels increase oxidative phosphorylation, independently of redox balance, mitochondrial membrane potential or calcium signalling. Kv1.3-induced respiration increased reactive oxygen species production. Reducing reactive oxygen concentrations inhibited Kv1.3-induced proliferation. Selective Kv1.3 mutation identified that channel-induced respiration required an intact voltage sensor and C-terminal ERK1/2 phosphorylation site, but is channel pore independent. We show Kv1.3 channels regulate respiration through a non-conducting mechanism to generate reactive oxygen species which drive proliferation. This study identifies a Kv1.3-mediated mechanism underlying the metabolic regulation of proliferation, which may provide a therapeutic target for diseases characterised by dysfunctional proliferation and cell growth.
Labels: MiParea: Respiration, nDNA;cell genetics
Organism: Human Tissue;cell: HEK Preparation: Intact cells
Coupling state: LEAK, ROUTINE, ET Pathway: CIV, ROX HRR: Oxygraph-2k