TITLE:
Mitochondrial Signaling in Hypoxia
AUTHORS:
Ludmila D. Lukyanova
KEYWORDS:
Respiratory Chain Reprogramming; Mitochondrial Complexes I and II; Adaptation to Hypoxia; Succinate; HIF-1; Energotropic Drugs; Antihypoxic Activity
JOURNAL NAME:
Open Journal of Endocrine and Metabolic Diseases,
Vol.3 No.2A,
May
20,
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 activity. The
review is focused on tactics and strategy for development of the antihypoxic defense and
antihypoxants with energotropic properties.