While fungi are widely occupying nature, many species are responsible for devastating mycosis in humans. Such niche diversity explains how quick fungal adaptation is necessary to endow the capacity of withstanding fluctuating environments and to cope with host-imposed conditions. Among all the molecular mechanisms evolved by fungi, the most studied one is the activation of the phosphorelay signalling pathways, of which the high osmolarity glycerol (HOG) pathway constitutes one of the key molecular apparatus underpinning fungal adaptation and virulence. In this review, we summarize the seminal knowledge of the HOG pathway with its more recent developments. We specifically described the HOG-mediated stress adaptation, with a particular focus on osmotic and oxidative stress, and point out some lags in our understanding of its involvement in the virulence of pathogenic species including, the medically important fungi Candida albicans, Cryptococcus neoformans, and Aspergillus fumigatus, compared to the model yeast Saccharomyces cerevisiae. Finally, we also highlighted some possible applications of the HOG pathway modifications to improve the fungal-based production of natural products in the industry.

Eukaryotic cells have evolved signalling pathways that allow adaptation to harmful conditions that disrupt endoplasmic reticulum (ER) homeostasis. When the function of the ER is compromised in a condition known as ER stress, the cell triggers the unfolded protein response (UPR) in order to restore ER homeostasis. Accumulation of misfolded proteins due to stress conditions activates the UPR pathway. In mammalian cells, the UPR is composed of three branches, each containing an ER sensor (PERK, ATF6 and IRE1). However, in yeast species, the only sensor present is the inositol-requiring enzyme Ire1. To cope with unfolded protein accumulation, Ire1 triggers either a transcriptional response mediated by a transcriptional factor that belongs to the bZIP transcription factor family or an mRNA degradation process. In this review, we address the current knowledge of the UPR pathway in several yeast species: Saccharomyces cerevisiae, Schizosaccharomyces pombe, Candida glabrata, Cryptococcus neoformans, and Candida albicans. We also include unpublished data on the UPR pathway of the budding yeast Kluyveromyces lactis. We describe the basic components of the UPR pathway along with similarities and differences in the UPR mechanism that are present in these yeast species.

Autophagy is a eukaryotic catabolic pathway that degrades and recycles cellular components to maintain homeostasis. It can target protein aggregates, superfluous biomolecular complexes, dysfunctional and damaged organelles, as well as pathogenic intracellular microbes. Autophagy is a dynamic process in which the different stages from initiation to final degradation of cargo are finely regulated. Therefore, the study of this process requires the use of a palette of techniques, which are continuously evolving and whose interpretation is not trivial. Here, we present the social amoeba Dictyostelium discoideum as a relevant model to study autophagy. Several methods have been developed based on the tracking and observation of autophagosomes by microscopy, analysis of changes in expression of autophagy genes and proteins, and examination of the autophagic flux with various techniques. In this review, we discuss the pros and cons of the currently available techniques to assess autophagy in this organism.

Tau is a microtubule-associated protein encoded by the MAPT gene and is mainly expressed in neurons. Alternative splicing generates preferentially six isoforms differing in N-terminal inserts (0, 1, or 2N) and microtubule-binding repeats (3R or 4R). Isoform expression varies by cell type, developmental stage, and neuronal maturation. Structurally, 4R isoforms bind and stabilize microtubules more effectively than 3R isoforms, while 3R variants are more prone to oligomerization. Differences among isoforms also affect aggregation and post-translational modification patterns, yet their specific roles in tauopathies remain unclear. Beyond its role in microtubule stabilization, tau is increasingly recognized for its functions in other cellular compartments, particularly mitochondria, where it may contribute to mitochondrial dysfunction in neurodegenerative diseases. Its intrinsically disordered conformation and extensive post-translational modifications enable interactions with multiple mitochondrial components, linking tau biology to broader aspects of neuronal health and pathology. The main focus of this review is to analyze how tau protein interacts with mitochondria and disrupts their function. Literature evidence indicates that tau localizes to the outer mitochondrial membrane, intermembrane space, and matrix, where it interferes with key processes. These include disruption of electron transport chain activity, inhibition of ATP synthase, and reduced ATP production, ultimately compromising neuronal energy supply. In parallel, tau destabilizes microtubule-based trafficking, impairing axonal transport and mitochondrial distribution, while also disrupting fission and fusion dynamics that shape mitochondrial morphology. Quality control pathways are affected as well, with tau altering mitophagy and mitochondria-nucleus signaling. Moreover, tau dysregulates calcium buffering and increases reactive oxygen species production, thereby promoting synaptic dysfunction, oxidative stress, and mitochondrial damage. Collectively, these facts establish tau as a central mediator of mitochondrial impairment and neuronal vulnerability. Elucidating the mechanisms by which tau affects mitochondrial physiology underscores its importance as a therapeutic target, with strategies aimed at preserving mitochondrial integrity offering promising avenues to slow neurodegenerative progression. In the last section, we include examples of clinical applications currently in various phases of testing, some of which show promising potential for implementation.