Heat shock protein 70 and ATP as partners in cell homeostasis (Review).
Heat shock proteins (HSP) are molecular chaperones, involved in many cellular functions such as protein folding, transport, maturation and degradation. Since they control the quality of newly synthesized proteins, HSP take part in cellular homeostasis. The Hsp70 family in particular exerts these functions in an adenosine triphosphate (ATP)-dependent manner. ATP is the main energy source used by cells to assume fundamental functions (respiration, proliferation, differentiation, apoptosis). Therefore, ATP levels have to be adapted to the requirements of the cells and ATP generation must constantly compensate ATP consumption. Nevertheless, under particular stress conditions, ATP levels decrease, threatening cell homeostasis and integrity. Cells have developed adaptive and protective mechanisms, among which Hsp70 synthesis and overexpression. In this review, we focus on the mechanisms which regulate Hsp70 expression under ATP depletion, using ischaemia as a paradigmatic model for ATP depletion in vivo, and analyze the molecular targets for Hsp70-mediated protection against ATP depletion. We also consider how these Hsp70-mediated protective effects could be applied in the therapeutical approaches of human diseases associated with cellular ATP depletion.
Mallouk
Y
Y
Laboratoire de Physiologie Respiratoire, Groupe Hospitalier et Universitaire Cochin-Port Royal, Universite Paris V, 75014 Paris, France.
Vayssier-Taussat
M
M
Bonventre
J V
JV
Polla
B S
BS
D000255:Adenosine Triphosphate / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000502:physiology*; D006801:Humans; D008928:Mitochondria / Q000201:enzymology; D018832:Molecular Chaperones / Q000378:metabolism; D010085:Oxidative Phosphorylation; D018384:Oxidative Stress / Q000502:physiology; D017510:Protein Folding; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D018832:Molecular Chaperones; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate