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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Biochem+Soc+Trans
2015 ; 43
(4
): 602-10
Nephropedia Template TP
gab.com Text
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English Wikipedia
The spatiotemporal regulation of the Keap1-Nrf2 pathway and its importance in
cellular bioenergetics
#MMPMID26551700
Dinkova-Kostova AT
; Baird L
; Holmström KM
; Meyer CJ
; Abramov AY
Biochem Soc Trans
2015[Aug]; 43
(4
): 602-10
PMID26551700
show ga
The Kelch-like ECH associated protein 1 (Keap1)-NF-E2 p45-related factor 2 (Nrf2)
pathway regulates networks of proteins that protect against the cumulative damage
of oxidants, electrophiles and misfolded proteins. The interaction between
transcription factor Nrf2 and its main negative cytoplasmic regulator Keap1
follows a cycle whereby the protein complex sequentially adopts two
conformations: 'open', in which Nrf2 binds to one monomer of Keap1, followed by
'closed', in which Nrf2 interacts with both members of the Keap1 dimer.
Electrophiles and oxidants (inducers) are recognized by cysteine sensors within
Keap1, disrupting its ability to target Nrf2 for ubiquitination and degradation.
Consequently, the protein complex accumulates in the 'closed' conformation, free
Keap1 is not regenerated and newly synthesized Nrf2 is stabilized to activate
target-gene transcription. The prevailing view of the Keap1-Nrf2 pathway, for
which there exists a wealth of experimental evidence, is that it lies at the
heart of cellular defence, playing crucial roles in adaptation and survival under
conditions of stress. More recently, the significance of Nrf2 in intermediary
metabolism and mitochondrial physiology has also been recognized, adding another
layer of cytoprotection to the repertoire of functions of Nrf2. One way by which
Nrf2 influences mitochondrial activity is through increasing the availability of
substrates (NADH and FADH2) for respiration. Another way is through accelerating
fatty acid oxidation (FAO). These findings reinforce the reciprocal relationship
between oxidative phosphorylation and the cellular redox state, and highlight the
key role of Nrf2 in regulating this balance.
|*Energy Metabolism
[MESH]
|Animals
[MESH]
|Humans
[MESH]
|Intracellular Signaling Peptides and Proteins/chemistry/*metabolism
[MESH]