Nathalia Chica Balaguera

• Balaguera, Nathalia Chica; Andersen, Aram Nikolai; Munoz, Sara Orellana; Llorente, Ignacio Garcia; P, Aurélie Nguéa & Nakken, Sigve [Show all 14 contributors for this article] (2026). Time-resolved functional genomics using deep learning reveals global hierarchical control of autophagy. Nature Cell Biology. ISSN 1465-7392. 28(3), p. 465–479. doi: 10.1038/s41556-025-01837-0. Full text in Research Archive Show summary

  Recycling of cellular components through autophagy maintains homeostasis in changing nutrient environments. Although its core mechanisms are extensively studied, understanding of its systems-wide dynamic regulation remains limited, particularly regarding how autophagy is inactivated once nutrients are restored. Here we mapped the genetic network that controls activation and inactivation of autophagy during nitrogen changes by combining time-resolved high-content imaging, deep learning and latent feature analysis. This dataset, termed AutoDRY, categorizes 5,919 mutants based on nutrient response kinetics and their contributions to autophagosome formation and clearance. Integrating these profiles with functional and genetic network data uncovered hierarchical and multilayered control of autophagy and revealed multiple new regulatory pathways. Notably, we identified the retrograde pathway as a pivotal time-varying modulator that tunes the expression of core autophagy genes and plays a central role in autophagy inactivation. Together, this study establishes a systems-level resource to guide future investigations of autophagy.

• Enserink, Jorrit Martijn & Balaguera, Nathalia Chica (2026). AutoDRY: a genome-wide resource revealing phase-specific control of autophagy activation, amplitude, and termination. Autophagy. ISSN 1554-8627. doi: 10.1080/15548627.2026.2660121. Full text in Research Archive
• Chica-Balaguera, Nathalia; Portantier, Marina; Nyquist-Andersen, Mari; Burriel, Silvia Espada & Aviles, Sandra Lopez (2022). Uncoupling of Mitosis and Cytokinesis Upon a Prolonged Arrest in Metaphase Is Influenced by Protein Phosphatases and Mitotic Transcription in Fission Yeast. Frontiers in Cell and Developmental Biology. 10. doi: 10.3389/fcell.2022.876810. Full text in Research Archive Show summary

  Depletion of the Anaphase-Promoting Complex/Cyclosome (APC/C) activator Cdc20 arrests cells in metaphase with high levels of the mitotic cyclin (Cyclin B) and the Separase inhibitor Securin. In mammalian cells this arrest has been exploited for the treatment of cancer with drugs that engage the spindle assembly checkpoint and, recently, with chemical inhibitors of the APC/C. While most cells arrested in mitosis for prolonged periods undergo apoptosis, others skip cytokinesis and enter G1 with unsegregated chromosomes. This process, known as mitotic slippage, generates aneuploidy and increases genomic instability in the cancer cell. Here, we analyze the behavior of fission yeast cells arrested in mitosis through the transcriptional silencing of the Cdc20 homolog slp1 . While depletion of slp1 readily halts cells in metaphase, this arrest is only transient and a majority of cells eventually undergo cytokinesis and show steady mitotic dephosphorylation. Notably, this occurs in the absence of Cyclin B (Cdc13) degradation. We investigate the involvement of phosphatase activity in these events and demonstrate that PP2A-B55 Pab1 is required to prevent septation and, during the arrest, its CDK-mediated inhibition facilitates the induction of cytokinesis. In contrast, deletion of PP2A-B56 Par1 completely abrogates septation. We show that this effect is partly due to this mutant entering mitosis with reduced CDK activity. Interestingly, both PP2A-B55 Pab1 and PP2A-B56 Par1 , as well as Clp1 (the homolog of the budding yeast mitotic phosphatase Cdc14) are required for the dephosphorylation of mitotic substrates during the escape. Finally, we show that the mitotic transcriptional wave controlled by the RFX transcription factor Sak1 facilitates the induction of cytokinesis and also requires the activity of PP2A-B56 Par1 in a mechanism independent of CDK.

• Klionsky, Daniel J.; Abdel-Aziz, Amal Kamal; Abdelfatah, Sara; Abdellatif, Mahmoud Khaled; Abdoli, Asghar & Abudu, Yakubu Princely [Show all 50 contributors for this article] (2021). Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition). Autophagy. ISSN 1554-8627. 17(1), p. 1–382. doi: https:/www.tandfonline.com/doi/full/10.1080/15548627.2020.1797280. Full text in Research Archive
• Martîn, Ruth Martîn; Portantier, Marina; Chica-Balaguera, Nathalia; Nyquist-Andersen, Mari; Mata, J & Lopez-Aviles, Sandra (2017). A PP2A-B55-Mediated Crosstalk between TORC1 and TORC2 Regulates the Differentiation Response in Fission Yeast. Current Biology. ISSN 0960-9822. 27(2), p. 175–188. doi: 10.1016/j.cub.2016.11.037. Full text in Research Archive Show summary

  Extracellular cues regulate cell fate, and this is mainly achieved through the engagement of specific transcriptional programs. The TORC1 and TORC2 complexes mediate the integration of nutritional cues to cellular behavior, but their interplay is poorly understood. Here, we use fission yeast to investigate how phosphatase activity participates in this interplay during the switch from proliferation to sexual differentiation. We find that loss of PP2A-B55Pab1 enhances the expression of differentiation-specific genes and leads to premature conjugation. pab1 deletion brings about a transcriptional profile similar to TORC1 inactivation, and deletion of pab1 overcomes the repression of differentiation genes in cells overexpressing TORC1. Importantly, we show that this effect is mediated by an increased TORC2-AKT (Gad8) signaling. Under nutrient-rich conditions, PP2A-B55Pab1 dephosphorylates Gad8 Ser546, repressing its activity. Conversely, TORC1 inactivation upon starvation leads to the inactivation of PP2A-B55Pab1 through the Greatwall-Endosulfin pathway. This results in the activation of Gad8 and the commitment to differentiation. Thus, PP2A-B55Pab1 enables a crosstalk between the two TOR complexes that controls cell-fate decisions in response to nutrient availability.

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