Heat shock response and autophagy—cooperation and control

Abstract

Abbreviations: AKT, v-akt murine thymoma viral oncogene homolog 1; AMPK, adenosine monophosphate-activated protein kinase; ATG, autophagy-related; BECN1, Beclin 1, autophagy related; EIF4EBP1, eukaryotic translation initiation factor 4E binding protein 1; ER, endoplasmic reticulum; FOXO, forkhead box O; HSF1, heat shock transcription factor 1; HSP, heat shock protein; HSPA8/ HSC70, heat shock 70kDa protein 8; IL, interleukin; LC3, MAP1LC3, microtubule-associated protein 1 light chain 3; MTMR14/ hJumpy, myotubularin related protein 14; MTOR, mechanistic target of rapamycin; NR1D1/Rev-Erb-a, nuclear receptor subfamily 1, group D, member 1; PBMC, peripheral blood mononuclear cell; PPARGC1A/PGC-1a, peroxisome proliferator-activated receptor, gamma, coactivator 1 a; RHEB, Ras homolog enriched in brain; SOD, superoxide dismutase; SQSTM1/p62, sequestosome 1; TPR, translocated promoter region, nuclear basket protein; TSC, tuberous sclerosis complex; ULK1, unc-51 like autophagy activating kinase 1.Protein quality control (proteostasis) depends on constant protein degradation and resynthesis, and is essential for proper homeostasis in systems from single cells to whole organisms. Cells possess several mechanisms and processes to maintain proteostasis. At one end of the spectrum, the heat shock proteins modulate protein folding and repair. At the other end, the proteasome and autophagy as well as other lysosome-dependent systems, function in the degradation of dysfunctional proteins. In this review, we examine how these systems interact to maintain proteostasis. Both the direct cellular data on heat shock control over autophagy and the time course of exercise-associated changes in humans support the model that heat shock response and autophagy are tightly linked. Studying the links between exercise stress and molecular control of proteostasis provides evidence that the heat shock response and autophagy coordinate and undergo sequential activation and downregulation, and that this is essential for proper proteostasis in eukaryotic systems.

Physiological regulation of the heat shock response by glutamine: implications for chronic low-grade inflammatory diseases in age-related conditions

“…However, mTORC1-S6K1 signal is critical for the regulation of cell cycle progression, cell size, and cell survival [232,263], so that reduction in intracellular glutamine stores may hamper cell survival. Recent studies have demonstrated that glutamine-assisted HS response may modulate autophagy, by regulating mTOR/Akt pathway and by blocking signaling pathways associated with protein degradation [41]. In cell culture, glutamine induces autophagy under basal and stressed conditions and prevents apoptosis under heat stress through its regulation of the mTOR and p38/MAP kinase pathways [57].…”

“…This is of note because many initiation transcription factor complexes (e.g., eIF2, eIF4F), which are assembled from multiple subunits, are sensitive to the activation by the mTOR cascade [233], thus resulting in coordinated protein synthesis and degradation [148]. Key intracellular proteins and transcriptional factors, such as Sp1 [54,231], are known to be O-GlcNAcylated via HBP during stress, injury, or illness, while phosphorylation of the eIF2 promotes the activation of HSF1 [41], leading to the expression of HSPs under stress conditions [56].…”

“…Therefore, the HS response and macroautophagy represent two ends of the spectrum of cellular protein quality control, with the former being ubiquitous in all living organisms, whereas the latter is restricted to eukaryotic cells [41]. During stress, increased levels of autophagy permit cells to adapt to changing nutritional and energy demands through protein catabolism [42].…”

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

“…In addition to the above, autophagy can solve therapy resistance and tumor relapse problems [24], take place in the heat shock response as well [25]. Autophagy is increased in many long lived model organisms and contributes significantly to their longevity [26].…”

“…Autophagy has emerged as a mediator in the pathogenesis of RA [23]. The dual fuction of autophagy is also embodied in cancer sites it removes damaged organelles to avoid the accumulation of oxygen free radicals and mutation, but limit cell necrosis and the spread of inflammation, helping tumor cells survive in metabolic stress and immune suppression at the same time.In addition to the above, autophagy can solve therapy resistance and tumor relapse problems [24], take place in the heat shock response as well [25]. Autophagy is increased in many long lived model organisms and contributes significantly to their longevity [26].…”