Stress resilience in plants: the complex interplay between heat stress memory and resetting

Abstract

Heat stress (HS) poses a major challenge to plants and agriculture, especially during climate change-induced heatwaves. Plants have evolved mechanisms to combat HS and remember past stress. This memory involves lasting changes in specific stress responses, enabling plants to better anticipate and react to future heat events. HS memory is a multi-layered cellular phenomenon that, in addition to epigenetic modifications, involves changes in protein quality control, metabolic pathways and broader physiological adjustments. An essential aspect of modulating stress memory is timely resetting, which restores defense responses to baseline levels and optimizes resource allocation for growth. Balancing stress memory with resetting enables plants to withstand stress while maintaining growth and reproductive capacity. In this review, we discuss mechanisms and regulatory layers of HS memory and resetting, highlighting their critical balance for enhancing stress resilience and plant fitness. We primarily focus on the model plant Arabidopsis thaliana due to the limited research on other species and outline key areas for future study.

Keywords: heat stress acclimation; memory; molecular mechanisms; plants; resetting.

Fig. 1

Model depicting plant responses to heat stress (HS) and the development of acquired thermotolerance through priming. Plants have an inherent ability, called basal thermotolerance, which allows them to withstand certain levels of heat stress (HS; represented by the orange star). However, when the severity of HS surpasses the plant's threshold, indicated by the red star, it results in plant death, while plants that have undergone priming (marked by the yellow star) exhibit different and more robust responses to subsequent severe HS. After priming, during the interval between the initial priming and a subsequent HS event, plants establish a form of stress memory. This memory involves selectively retaining certain stress‐related changes that are advantageous for future stress responses while resetting others for normal growth. Achieving a balance between maintaining stress memory and resetting these changes is vital for the plant's survival, growth and productivity. Full resetting may impair the plant's ability to respond to subsequent stress, whereas continuous activation of all priming responses could hinder growth. The figure depicts three possible responses to HS after priming: continuous priming, leading to sustained readiness against future stress; full resetting, which returns the plant to its original prestress state; and a balanced response, allowing optimal recovery while retaining some level of readiness. The triangular gradient in the figure represents increasing HS severity from low to high. Created in BioRender. Bz, S. (2025) https://BioRender.com/n88r065.

Fig. 2

Major components involved in heat stress memory (HSM) and resetting across different regulatory levels. This diagram categorizes the molecular components associated with either stress memory (red arrows) or stress resetting (blue arrows) in four distinct layers of regulation in Arabidopsis: transcriptional and post‐transcriptional regulation, epigenetic regulation, control of proteome integrity and metabolic/hormonal reprogramming. Specific components are listed under each category to illustrate their role in stress response mechanisms. It is important to note that components within each layer may influence other regulatory levels as well. HSFA1s, Heat Shock Factor A1s; HSFA2, Heat Shock Factor A2; HSFA3, Heat Shock Factor A3; FGT3, FORGETTER 3; HSFA7b, Heat Shock Factor A7b; BES1, BRI1 EMS‐SUPPRESSOR 1; E2Fa, transcription factor E2Fa; EIN3, ETHYLENE INSENSITIVE 3; AGO1, ARGONAUTE1; miR156, microRNA156; AtXRN4, Arabidopsis 5'‐3' EXORIBONUCLEASE 4; CSN5A, CONSTITUTIVE PHOTOMORPHOGENESIS 5A; ATAF1, Arabidopsis NAC (NAM, ATAF and CUC) domain‐containing protein ATAF1; ANAC055, Arabidopsis NAC (NAM, ATAF and CUC) transcription factor 055; FGT1, FORGETTER 1; SWI/SNF (BRAHMA), SWItch/Sucrose Nonfermenting with its component BRAHMA; ISWI (CHR11, CHR17), Imitation SWItch with its components Chromatin Remodeling Protein 11 and 17; CDK8, CYCLIN‐DEPENDENT KINASE 8; Med12, MEDIATOR 12; BRU1, Brushy1; JMJs (11, 12, 30 & 32), JUMONJI demethylases 11, 12, 30 and 32; HLP1, HIKESHI‐LIKE PROTEIN 1; HSP21, Heat shock protein 21; HSA32, Heat Stress‐Associated 32 kDa Protein; HSP101, Heat shock protein 101; HSP90‐1, Heat shock protein 90‐1; ROF1, ROTAMASE 1; FtsH6, Filamentous Temperature‐Sensitive H6; NBR1, NEXT‐TO‐BRCA1; ATI1, ATG8‐INTERACTING PROTEIN 1; PLDα2, PHOSPHOLIPASE D ALPHA 2; FGT2, FORGETTER 2; APD9, Arabidopsis PP2C Clade D9 protein; P2C79, protein phosphatase 2C 79; TOR, TARGET OF RAPAMYCIN; FBA6, FRUCTOSE‐BISPHOSPHATE ALDOLASE 6. Created in BioRender. Bz, S. (2025) https://BioRender.com/c08l459.

Fig. 3

Transcriptional regulation of heat stress memory (HSM) genes upon (priming) HS. (a) HSFA2‐dependent transcriptional regulation of HSM genes in Arabidopsis. (i) Transcriptional regulation of HSFA2: (priming) HS and other environmental factors, such as Enterobacter sp. SA187 trigger different signaling cascades involving ETHYLENE INSENSITIVE3 (EIN3), TARGET OF RAPAMYCIN (TOR) or nitric oxide (NO)–S‐nitrosoglutathione (GSNO) to activate HSFA2 transcription. This involves transcription factors like ERF95/97, E2Fa which is phosphorylated (‘P’) by TOR, and GT‐1, which is activated by S‐nitrosylation (‘SNO’). Furthermore, retrograde signaling via GUN5 plays a role in regulating HSFA2 expression in response to HS. However, the precise molecular details of how GUN5 influences HSFA2 transcription through retrograde signaling remain to be fully identified. (ii) Regulation of HSM genes by HSFA2: The HSFA2‐HSF complex binds to target HSM gene promoters. At these promoters, chromatin modifications, such as H3K4me3 methylation occur, which mark the genes for active transcription. HSFA2 directly binds to CDK8 and recruits the mediator complex to HSM genes, where it coordinates the activity of RNA polymerase II. Proteins like HSP90 and ROF1 form a complex with HSFA2 and enhance its transcriptional activity toward target genes. ‘A2’, ‘A3’ and ‘Ax’ indicate HSFA2, HSFA3 and other HSFs participating in complex formation. (b) Regulation of HSM genes by BES1 in Arabidopsis. BR‐induced inhibition of BIN2 kinase and (priming) HS trigger the dephosphorylation of BES1 and increase its nuclear abundance. Activated BES1 binds to the promoters of HSM genes, promoting their sustained activation. This regulatory process involves the demethylation of H3K27me3. Additionally, HS activates BES1 through ABA‐repressed PP2C phosphatases, such as ABI1. Activated BES1 then interacts with HSFA1s, binding to HEAT SHOCK ELEMENTS (HSEs) within the promoters of HSP70 and HSP90 genes, which induces their expression and enhances HS resistance. It remains to be determined whether the BES1‐HSFA1s complex also binds HSM genes highlighted by a question mark. Dotted lines depict processes or interactions for which the exact mechanisms are not fully elucidated. ABA, abscisic acid; ABI1, ABA INSENSITIVE 1; BES1, BRI1 EMS‐SUPPRESSOR 1; BIN2, BRASSINOSTEROID‐INSENSITIVE 2; BR, brassinosteroids; CDK8, CYCLIN‐DEPENDENT KINASE 8; ERFs, ethylene response factors; ERF95, Ethylene Response Factor 95; ERF97, Ethylene Response Factor 97; E2Fa, transcription factor E2Fa; GT‐1, trihelix transcription factor GT‐1; GUN5, GENOMES UNCOUPLED 5; HS, heat stress; HSF, heat shock factor; HSFA1s, Heat Shock Factor A1s; HSFA2, HEAT SHOCK FACTOR A2; HSFA2‐I, HSFA2 splice variant I, encoding the full‐length protein; HSFA2‐III, HSFA2 splice variant III, encoding the truncated protein S‐HSFA2; HSP70, Heat Shock Protein 70; HSP90, Heat Shock Protein 90; H3K4me3, histone H3 ‐ lysine 4 trimethylated; H3K27me3, histone 4 ‐ lysine 27 trimethylated; Med12, MEDIATOR 12; MKM, mediator kinase module; PP2C, protein phosphatase type 2C; RNA Pol II, RNA polymerase II; ROF1, ROTAMASE 1; S‐HSFA2, truncated HSFA2 protein. Figure assembled from part figures created in BioRender. Bz, S. (2025) https://BioRender.com/a09a574, Bz, S. (2025) https://BioRender.com/s35t757, and Bz, S. (2025) https://BioRender.com/a23i343.

Fig. 4

Simplified model summarizing mechanisms of heat stress (HS) resetting and their connection to HS memory (HSM). In Arabidopsis, HSFA2 activates memory genes (e.g. HSA32 and HSP21) that promote and maintain HSM, and activates the memory gene involved in resetting, FTSH6. During recovery, the resetting of HSFA2 transcripts involves mechanisms like mRNA decay via XRN4. Additionally, the COP9 signalosome subunit CSN5A aids in transcriptional resetting by downregulating HSM gene expression (e.g. APX2 and HSP22; not specified in the figure), potentially through altered H3K4me3 methylation, a process that requires further investigation. Protein degradation is also crucial: the plastidial metalloprotease FtsH6 degrades HSP21 to limit memory duration. Autophagy, mediated by NBR1 and ATI1 receptors, target key chaperones like HSP101, HSP90‐ROF1 and HSP21. The degradation of HSP90‐ROF1 impacts HSFA2 activity and its transcriptional regulation of target genes. Transcription factors ATAF1 and ANAC055, which are linked to autophagy regulation, are involved in stress resetting, as their mutants show improved memory retention. This network of transcriptional and post‐translational mechanisms suggests how plants balance HSM and resetting for both effective stress response and resumption of growth. Arrow‐ending lines indicate positive, and T‐ending lines negative interactions, respectively. ANAC055, Arabidopsis NAC (NAM, ATAF and CUC) transcription factor 055; APX2, ASCORBATE PEROXIDASE 2; ATAF1, Arabidopsis NAC (NAM, ATAF and CUC) domain containing protein ATAF1; ATGs, AUTOPHAGY RELATED GENES; ATI1, ATG8‐INTERACTING PROTEIN 1; CSN5A, CONSTITUTIVE PHOTOMORPHOGENESIS 5A; FtsH6, Filamentous Temperature‐Sensitive H6 protein; FTSH6, FILAMENTOUS TEMPERATURE‐SENSITIVE H6 gene; HSA32, Heat Stress‐Associated 32 kDa Protein; HSFA2, Heat Shock Factor A2; HSP21, Heat Shock Protein 21; HSP22, Heat Shock Protein 22; HSP90, Heat Shock Protein 90; HSP101, Heat Shock Protein 101; H3K4me3, histone H3 ‐ lysine 4 trimethylation; NBR1, NEXT‐TO‐BRCA1; ROF1, ROTAMASE 1; TFs, transcription factors; XRN4, 5'‐3' EXORIBONUCLEASE 4. Created in BioRender. Bz, S. (2025) https://BioRender.com/g63v207.

Fig. 5

Schematic representation of signaling pathways involved in heat stress memory (HSM) at the shoot apex. Glucose signaling activates the TARGET OF RAPAMYCIN (TOR) pathway, leading to phosphorylation (‘P’) of E2Fa, which then activates HLP1 to promote histone modifications (H3K4me3 and H3K acetylations, H3K9, H3K14, H3K18, H3K23 and H3K27) at HS gene promoters in Arabidopsis. E2Fa also binds to the promoters of HSFA1s and HSFA2 to activate their expression, leading to elevated expression of HSPs and enhanced carbohydrate metabolism through FBA6, contributing to high energy/carbon status and HSM. Glucose‐TOR‐regulated E2Fa also enhances H3K4me3 methylation at memory loci by inducing ATX1. Furthermore, the TOR substrate HISTONE ACETYLTRANSFERASE 1 (HAC1) regulates the expression of HS‐responsive genes by modulating acetylation at their promoter regions. Additionally, ethylene activates HSFA7b and ETHYLENE INSENSITIVE3 (EIN3). EIN3 promotes the expression of ethylene‐regulated genes, further contributing to the plant's HS adaptation. HSFA7b activates the ethylene biosynthesis repressors ETO1 and EOL1 to ensure ethylene homeostasis at the SAM. Arrow‐ending lines indicate positive, and T‐ending lines negative interactions, respectively. The dotted line indicates change in glucose availability by FBA6. ATX1, ARABIDOPSIS TRITHORAX 1; C, carbon; EOL1, ETO1‐LIKE 1; ETO1, ETHYLENE OVERPRODUCER 1; E2Fa, transcription factor E2Fa; FBA6, FRUCTOSE‐BISPHOSPHATE ALDOLASE 6; HLP1, HIKESHI‐LIKE PROTEIN 1; HS, heat stress; HSFA1s, Heat Shock Factor A1s; HSFA2, Heat Shock Factor A2; HSFA7b, Heat Shock Factor A7b; HSPs, heat shock proteins; H3K, histone 3 lysine; H3K4me3, histone H3 ‐ lysine 4 trimethylation; H3K9, H3K14, H3K18, H3K23, H3K27, histone 3, acetylated at lysine 9, 14, 18, 23, or 27, respectively; TOR, TARGET OF RAPAMYCIN. Created in BioRender. Bz, S. (2025) https://BioRender.com/p86j616.

Fig. 6

Future research directions for studying heat stress memory (HSM) and resetting in plants. (a) Molecular and biochemical mechanisms to investigate the role of proteins and gene expression in HSM, using advanced techniques like ribosome profiling, proteomics and microscopy. (b) Spatial and temporal control: studying the spatial and temporal dynamics of HSM and its impact on plant productivity and yield. (c) Balance between memory and resetting: understanding the trade‐offs between stress memory and stress resetting in relation to plant survival, growth and yield. (d) Natural accessions: leveraging natural plant accessions and genome‐wide association studies (GWAS) to explore genetic diversity, phenotyping for HSM and integrating multi‐omics data for functional validation. (e) Beyond Arabidopsis: translating findings from model plants like Arabidopsis to crops, with a focus on phenotyping, multi‐omics and genome editing. (f) Natural settings: Extending research from controlled laboratory environments to (semi)‐field and natural conditions to better understand HSM in realistic agricultural settings. HS, heat stress; LLPS, liquid‐liquid phase separation. Question marks indicate processes that need to be studied further in future research. The dotted line in panel (b) indicates the progression through different stages in plant development. Created in BioRender. Bz, S. (2024) https://BioRender.com/r76n900.