Response to hyperthermia, highly conserved from bacteria to humans, involves transcriptional upregulation of genes involved in battling the cytotoxicity caused by misfolded and denatured proteins, with the aim of proteostasis restoration. C. elegans senses and responds to changes in growth temperature or noxious thermal stress by well-defined signaling pathways. Under adverse conditions, regulation of the heat shock response (HSR) in C. elegans is controlled by a single transcription factor, heat-shock factor 1 (HSF-1). HSR and HSF-1 in particular are proven to be central to survival under proteotoxic stress, with additional roles in normal physiological processes. For years, it was a common belief that upregulation of heat shock proteins (HSPs) by HSF-1 was the main and most important step toward thermotolerance. However, an ever-growing number of studies have shown that targets of HSF-1 involved in cytoskeletal and exoskeletal integrity preservation as well as other HSF-1 dependent and independent pathways are equally important. In this review, we follow the thermal stimulus from reception by the nematode nerve endings till the activation of cellular response programs. We analyze the different HSF-1 functions in HSR as well as all the recently discovered mechanisms that add to the knowledge of the heat stress coping network of C. elegans.

In animals mtDNA inheritance is maternal except in certain molluscan bivalve species which have a paternally inherited mitochondrial genome (genome M) along with the standard maternal one (genome F). Normally, the paternal genome occurs in the male gonad, but it can be often found, as a minority, in somatic tissues of males and females. This may happen in two ways. One is through "sperm mtDNA leakage" into somatic tissues, a deviation from the normal situation in which the sperm mtDNA vanishes in females or ends up exclusively in the germ line of males. The other is through "egg heteroplasmy", when the egg contains, in small quantities, the paternal genome in addition to maternal genome.

P38 Mitogen-Activated Protein Kinase (MAPK) cascades are central regulators of numerous physiological cellular processes, including stress response signaling. In C. elegans, mitochondrial dysfunction activates a PMK-3/p38 MAPK signaling pathway (MAPK^mt), but its functional role still remains elusive. Here, we demonstrate the induction of MAPK^mt in worms deficient in the lonp-1 gene, which encodes the worm ortholog of mammalian mitochondrial LonP1. This induction is subjected to negative regulation by the ATFS-1 transcription factor through the CREB-binding protein (CBP) ortholog CBP-3, indicating an interplay between both activated MAPK^mt and mitochondrial Unfolded Protein Response (UPR^mt) surveillance pathways. Our results also reveal a genetic interaction in lonp-1 mutants between PMK-3 kinase and the ZIP-2 transcription factor. ZIP-2 has an established role in innate immunity but can also modulate the lifespan by maintaining mitochondrial homeostasis during ageing. We show that in lonp-1 animals, ZIP-2 is activated in a PMK-3-dependent manner but does not confer increased survival to pathogenic bacteria. However, deletion of zip-2 or pmk-3 shortens the lifespan of lonp-1 mutants, suggesting a possible crosstalk under conditions of mitochondrial perturbation that influences the ageing process. Furthermore, loss of pmk-3 specifically diminished the extreme heat tolerance of lonp-1 worms, highlighting the crucial role of PMK-3 in the heat shock response upon mitochondrial LONP-1 inactivation.

Background: Marine mussels (Mytilus spp.) exhibit a mitochondrial DNA (mtDNA) inheritance system known as doubly uniparental inheritance (DUI), in which maternally and paternally transmitted genomes coexist and are independently inherited. One model proposes that M-type mtDNA forms a complex with a nuclear-encoded masculinising protein, based on an electrophoretic mobility shift observed with an M-type control-region probe and male gonadal extracts. A prediction is that this protein should be preferentially enriched with the M-type probe in male gonads and fertilised eggs from male-biased females, compared with corresponding female and F-type probe controls. Methods: We tested this prediction in Mytilus galloprovincialis using electrophoretic mobility shift assays (EMSA) with biotin-labelled M- and F-type probes, and quantitative shotgun proteomics of pull-down fractions using TMT10plex labelling and LC-MS/MS. Results: EMSA did not detect the expected mtDNA-protein complex, and proteomics identified no statistically significant protein enrichment consistent with model predictions in either gonads or eggs. Conclusions: Although these results do not support the attachment hypothesis under the conditions tested, they provide empirical constraints on a key mechanistic model and highlight the need for complementary approaches, including perinuclear protein enrichment strategies, to resolve the molecular basis of sex determination and paternal mtDNA transmission in bivalves with DUI.