TITLE:
Mitochondrial Signaling in Hypoxia
AUTHORS:
L. D. Lukyanova
KEYWORDS:
Respiratrory Chain Reprogramming; Mitochondrial Complexes I and II; Adaptation to Hypoxia; Succinate; HIF-1; Energotropic Drugs; Antihypoxic Activitie
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.3 No.3,
July
12,
2013
ABSTRACT: This paper focuses on a bioenergetic mechanism
responding to hypoxia. This response involves hypoxia-induced reprogramming of respiratory
chain function and switching from oxidation of complex I (NAD-related substrates)
to complex II (succinate oxidation). Transient, reversible, compensatory activation
of respiratory chain complex II is a major mechanism of urgent adaptation to hypoxia,
which is necessary for 1) succinate-related energy synthesis in the conditions of
oxygen shortage and formation of urgent resistance; 2) succinate-related stabilization
of HIF-1α and initiation of its transcriptional activity related with formation
of long-term adaptation; 3) succinate-dependent activation of the succinate-specific
receptor GPR91. Thus, mitochondria perform a signaling function with succinate as
a signaling molecule. Effects of succinate in hypoxia occur at three levels, intramitochondrial, intracellular
and intercellular. In these settings, succinate displays antihypoxic activitie.
The review is focused on tactics and strategy for development of the antihypoxic defense and antihypoxants
with energotropic properties.