Suppression of mitochondrial respiration by hydrogen sulfide in hibernating 13-lined ground squirrels

TY - JOUR

T1 - Suppression of mitochondrial respiration by hydrogen sulfide in hibernating 13-lined ground squirrels

AU - Jensen, Birgitte S.

AU - Pardue, Sibile

AU - Duffy, Brynne

AU - Kevil, Christopher G.

AU - Staples, James F.

AU - Fago, Angela

PY - 2021/6

Y1 - 2021/6

N2 - Hibernating mammals may suppress their basal metabolic rate during torpor by up to 95% to reduce energy expenditure during winter, but the underlying mechanisms remain poorly understood. Here we show that hydrogen sulfide (H2S), a ubiquitous signaling molecule, is a powerful inhibitor of respiration of liver mitochondria isolated from torpid 13-lined ground squirrels, but has a weak effect on mitochondria isolated during summer and hibernation arousals, where metabolic rate is normal. Consistent with these in vitro effects, we find strong seasonal variations of in vivo levels of H2S in plasma and increases of H2S levels in the liver of squirrels during torpor compared to levels during arousal and summer. The in vivo changes of liver H2S levels correspond with low activity of the mitochondrial H2S oxidizing enzyme sulfide:quinone oxidoreductase (SQR) during torpor. Taken together, these results suggest that during torpor, H2S accumulates in the liver due to a low SQR activity and contributes to inhibition of mitochondrial respiration, while during arousals and summer these effects are reversed, H2S is degraded by active SQR and mitochondrial respiration rates increase. This study provides novel insights into mechanisms underlying mammalian hibernation, pointing to SQR as a key enzyme involved in the control of mitochondrial function.

AB - Hibernating mammals may suppress their basal metabolic rate during torpor by up to 95% to reduce energy expenditure during winter, but the underlying mechanisms remain poorly understood. Here we show that hydrogen sulfide (H2S), a ubiquitous signaling molecule, is a powerful inhibitor of respiration of liver mitochondria isolated from torpid 13-lined ground squirrels, but has a weak effect on mitochondria isolated during summer and hibernation arousals, where metabolic rate is normal. Consistent with these in vitro effects, we find strong seasonal variations of in vivo levels of H2S in plasma and increases of H2S levels in the liver of squirrels during torpor compared to levels during arousal and summer. The in vivo changes of liver H2S levels correspond with low activity of the mitochondrial H2S oxidizing enzyme sulfide:quinone oxidoreductase (SQR) during torpor. Taken together, these results suggest that during torpor, H2S accumulates in the liver due to a low SQR activity and contributes to inhibition of mitochondrial respiration, while during arousals and summer these effects are reversed, H2S is degraded by active SQR and mitochondrial respiration rates increase. This study provides novel insights into mechanisms underlying mammalian hibernation, pointing to SQR as a key enzyme involved in the control of mitochondrial function.

KW - H2S

KW - Hypometabolism

KW - Ictidomys tridecemlineatus

KW - sulfide:quinone oxidoreductase

KW - Torpor

KW - METABOLIC SUPPRESSION

KW - NITRIC-OXIDE

KW - THIOSULFATE

KW - INHIBITION

KW - OXIDATION

KW - CYANIDE

KW - TORPOR

KW - BLOOD

KW - CELLS

KW - LIVER

U2 - 10.1016/j.freeradbiomed.2021.04.009

DO - 10.1016/j.freeradbiomed.2021.04.009

M3 - Journal article

C2 - 33887435

SN - 0891-5849

VL - 169

SP - 181

EP - 186

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

ER -