Plasma membranes as heat stress sensors: From lipid-controlled molecular switches to therapeutic applications

László Vigh, Zsolt Török, Tim Crul, Bruno Maresca, Gerhard J. Schütz, Felix Viana, Laura Dindia, Stefano Piotto, Mario Brameshuber, Gábor Balogh, Mária Péter, Amalia Porta, Alfonso Trapani, Imre Gombos, Attila Glatz, Burcin Gungor, Begüm Peksel, László Vigh, Bálint Csoboz, Ibolya HorváthMathilakath M. Vijayan, Phillip L. Hooper, John L. Harwood

Research output: Contribution to journalReview article

50 Citations (Scopus)


The classic heat shock (stress) response (HSR) was originally attributed to protein denaturation. However, heat shock protein (Hsp) induction occurs in many circumstances where no protein denaturation is observed. Recently considerable evidence has been accumulated to the favor of the "Membrane Sensor Hypothesis" which predicts that the level of Hsps can be changed as a result of alterations to the plasma membrane. This is especially pertinent to mild heat shock, such as occurs in fever. In this condition the sensitivity of many transient receptor potential (TRP) channels is particularly notable. Small temperature stresses can modulate TRP gating significantly and this is influenced by lipids. In addition, stress hormones often modify plasma membrane structure and function and thus initiate a cascade of events, which may affect HSR. The major transactivator heat shock factor-1 integrates the signals originating from the plasma membrane and orchestrates the expression of individual heat shock genes. We describe how these observations can be tested at the molecular level, for example, with the use of membrane perturbers and through computational calculations. An important fact which now starts to be addressed is that membranes are not homogeneous nor do all cells react identically. Lipidomics and cell profiling are beginning to address the above two points. Finally, we observe that a deregulated HSR is found in a large number of important diseases where more detailed knowledge of the molecular mechanisms involved may offer timely opportunities for clinical interventions and new, innovative drug treatments. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy.

Original languageEnglish
Pages (from-to)1594-1618
Number of pages25
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number6
Publication statusPublished - Jun 2014



  • Cell-to-cell heterogeneity
  • Heat shock response
  • Lipid raft
  • Lipidomics
  • Membrane lipid therapy
  • Stress hormone
  • TRP channel

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

Cite this

Vigh, L., Török, Z., Crul, T., Maresca, B., Schütz, G. J., Viana, F., Dindia, L., Piotto, S., Brameshuber, M., Balogh, G., Péter, M., Porta, A., Trapani, A., Gombos, I., Glatz, A., Gungor, B., Peksel, B., Vigh, L., Csoboz, B., ... Harwood, J. L. (2014). Plasma membranes as heat stress sensors: From lipid-controlled molecular switches to therapeutic applications. Biochimica et Biophysica Acta - Biomembranes, 1838(6), 1594-1618.