The C. elegans mitochondrial K+ATP channel: A potential target for preconditioning

Wojtovich, Andrew P.; Burwell, Lindsay S.; Sherman, Teresa; Nehrke, Keith; Brookes, Paul S.

doi:10.1016/j.bbrc.2008.09.043

Cited by 28 publications

(34 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The pharmacology of mitoK ATP is conserved in humans [137], rats [79], plants [138], amoeba [139], trypanosomes [140], and C. elegans [141], and remains the default method to assign a role for mitoK ATP in IR protection. A catalog of K + channel pharmacophores applicable to mitochondrial research is given in Table 1.…”

Section: Mitochondrial Katp Channel: Composition Pharmacology Regulmentioning

confidence: 99%

The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection

Smith

Nehrke

Brookes

2017

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

Mitochondria play an important role in tissue ischemia and reperfusion (IR) injury, with energetic failure and the opening of the mitochondrial permeability transition pore being the major causes of IR-induced cell death. Thus, mitochondria are an appropriate focus for strategies to protect against IR injury. Two widely studied paradigms of IR protection, particularly in the field of cardiac IR, are ischemic preconditioning (IPC) and volatile anesthetic preconditioning (APC). While the molecular mechanisms recruited by these protective paradigms are not fully elucidated, a commonality is the involvement of mitochondrial K+ channel opening. In the case of IPC, research has focused on a mitochondrial ATP-sensitive K+ channel (mitoKATP), but, despite recent progress, the molecular identity of this channel remains a subject of contention. In the case of APC, early research suggested the existence of a mitochondrial large-conductance K+ (BK, big conductance of potassium) channel encoded by the Kcnma1 gene, although more recent work has shown that the channel that underlies APC is in fact encoded by Kcnt2. In this review, we discuss both the pharmacologic and genetic evidence for the existence and identity of mitochondrial K+ channels, and the role of these channels both in IR protection and in regulating normal mitochondrial function.

show abstract

Section: Mitochondrial Katp Channel: Composition Pharmacology Regulmentioning

confidence: 99%

The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection

Smith

Nehrke

Brookes

2017

Biochemical Journal

Self Cite

View full text Add to dashboard Cite

show abstract

“…MitoK ATP activity was identified also in mitochondria of the nematode worm Caenorhabditis elegans [194]. Furthermore, in plant mitochondria, which possess a very active K + cycle, a K + uniport pathway with characteristics of mitoKATP has been observed to sustain an ion flow sufficient to uncouple respiration [38, 95,141,142].…”

Section: The Mitochondrial Atp-dependent Potassium Channelmentioning

confidence: 99%

Physiology of potassium channels in the inner membrane of mitochondria

Szabó

Leanza

Gulbins

et al. 2011

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

The inner membrane of the ATP-producing organelles of endosymbiotic origin, mitochondria, has long been considered to be poorly permeable to cations and anions, since the strict control of inner mitochondrial membrane permeability is crucial for efficient ATP synthesis. Over the past 30 years, however, it has become clear that various ion channels--along with antiporters and uniporters--are present in the mitochondrial inner membrane, although at rather low abundance. These channels are important for energy supply, and some are a decisive factor in determining whether a cell lives or dies. Their electrophysiological and pharmacological characterisations have contributed importantly to the ongoing elucidation of their pathophysiological roles. This review gives an overview of recent advances in our understanding of the functions of the mitochondrial potassium channels identified so far. Open issues concerning the possible molecular entities giving rise to the observed activities and channel protein targeting to mitochondria are also discussed.

show abstract

“…Our own work has shown that worm mitochondria, like those from mammals, have both K ATP and big conductance potassium (BK) channels whose activities appear to be both necessary and sufficient for protection from ischemic damage (Wojtovich et al, 2008). Interestingly, metabolic profiling in worms with Ox-Phos mutations suggests a transition to alternate means of ATP production that do not require O 2 , and these worms are both long-lived and resistant to ischemia (Butler et al, 2010; Rea et al, 2007).…”

Section: Current Researchmentioning

confidence: 99%

Ischemic preconditioning: The role of mitochondria and aging

Wojtovich

Nadtochiy

Brookes

et al. 2012

Experimental Gerontology

Self Cite

View full text Add to dashboard Cite

Aging represents a triple threat for myocardial infarction (MI). Not only does the incidence of MI increase with age, but the heart becomes more susceptible to MI induced damage and protective interventions such as ischemic preconditioning (IPC) become less effective. Therefore, any rational therapeutic strategy must be built around the ability to combat the detrimental effects of ischemia in aged individuals. To accomplish this, we need to develop a better understanding of how ischemic damage, protection, and aging are linked. In this regard, mitochondria have emerged as a common theme. First, mitochondria contribute to cell damage during ischemia-reperfusion (IR), and are central to cell death. Second, the protective signaling pathways activated by IPC converge on mitochondria, and the opening of mitochondrial ion channels alone is sufficient to elicit protection. Finally, mitochondria clearly influence the aging process and specific defects in mitochondrial activity are associated with age-related functional decline. This review will summarize the effects of aging on myocardial IR injury and discuss relevant and emerging strategies to protect against MI with an emphasis on mitochondrial function.

show abstract

The C. elegans mitochondrial K+ATP channel: A potential target for preconditioning

Cited by 28 publications

References 43 publications

The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection

The Slo(w) path to identifying the mitochondrial channels responsible for ischemic protection

Physiology of potassium channels in the inner membrane of mitochondria

Ischemic preconditioning: The role of mitochondria and aging

Contact Info

Product

Resources

About