TY - JOUR AB - Ferroptosis is a necrotic, non-apoptotic cell death modality triggered by unrestrained iron-dependent lipid peroxidation. By unveiling the regulatory mechanisms of ferroptosis and its relevance to various diseases, research over the past decade has positioned ferroptosis as a promising therapeutic target. The rapid growth of this research field presents challenges, associated with potentially inadequate experimental approaches that may lead to misinterpretations in the assessment of ferroptosis. Typical examples include assessing whether an observed phenotype is indeed linked to ferroptosis, and selecting appropriate animal models and small-molecule modulators of ferroptotic cell death. This Expert Recommendation outlines state-of-the-art methods and tools to reliably study ferroptosis and increase the reproducibility and robustness of experimental results. We present highly validated compounds and animal models, and discuss their advantages and limitations. Furthermore, we provide an overview of the regulatory mechanisms and the best-studied players in ferroptosis regulation, such as GPX4, FSP1, SLC7A11 and ACSL4, discussing frequent pitfalls in experimental design and relevant guidance. These recommendations are intended for researchers at all levels, including those entering the expanding and exciting field of ferroptosis research. AU - Mishima, E. AU - Nakamura, T. AU - Doll, S. AU - Proneth, B. AU - Fedorova, M.* AU - Pratt, D.A.* AU - Friedmann Angeli, J.P.* AU - Dixon, S.J.* AU - Wahida, A. AU - Conrad, M. C1 - 74043 C2 - 57306 CY - Heidelberger Platz 3, Berlin, 14197, Germany TI - Recommendations for robust and reproducible research on ferroptosis. JO - Nat. Rev. Mol. Cell Biol. PB - Nature Portfolio PY - 2025 SN - 1471-0072 ER - TY - JOUR AU - Zong, Z. C1 - 73298 C2 - 56996 CY - Heidelberger Platz 3, Berlin, 14197, Germany TI - Expanding the genetic code for site-specific lysine lactylation. JO - Nat. Rev. Mol. Cell Biol. VL - 26 PB - Nature Portfolio PY - 2025 SN - 1471-0072 ER - TY - JOUR AB - In mammals, hundreds of proteins use iron in a multitude of cellular functions, including vital processes such as mitochondrial respiration, gene regulation and DNA synthesis or repair. Highly orchestrated regulatory systems control cellular and systemic iron fluxes ensuring sufficient iron delivery to target proteins is maintained, while limiting its potentially deleterious effects in iron-mediated oxidative cell damage and ferroptosis. In this Review, we discuss how cells acquire, traffick and export iron and how stored iron is mobilized for iron–sulfur cluster and haem biogenesis. Furthermore, we describe how these cellular processes are fine-tuned by the combination of various sensory and regulatory systems, such as the iron-regulatory protein (IRP)–iron-responsive element (IRE) network, the nuclear receptor co-activator 4 (NCOA4)-mediated ferritinophagy pathway, the prolyl hydroxylase domain (PHD)–hypoxia-inducible factor (HIF) axis or the nuclear factor erythroid 2-related factor 2 (NRF2) regulatory hub. We further describe how these pathways interact with systemic iron homeostasis control through the hepcidin–ferroportin axis to ensure appropriate iron fluxes. This knowledge is key for the identification of novel therapeutic opportunities to prevent diseases of cellular and/or systemic iron mismanagement. AU - Galy, B.* AU - Conrad, M. AU - Muckenthaler, M.* C1 - 68193 C2 - 54818 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 133–155 TI - Mechanisms controlling cellular and systemic iron homeostasis. JO - Nat. Rev. Mol. Cell Biol. VL - 25 PB - Nature Portfolio PY - 2024 SN - 1471-0072 ER - TY - JOUR AB - Correction to: Nature Reviews Molecular Cell Biologyhttps://doi.org/10.1038/s41580-023-00648-1, published online 2 October 2023 In the version of the article initially published, the last sentence of the “Iron transfer to the mitochondrion” section, “However, counterintuitively, MCU1 deficiency in myeloid cells leads to mitochondrial iron accumulation, not depletion”, was incorrect and so has now been removed along with the corresponding reference. This correction has been made to the HTML and PDF versions of the article. AU - Galy, B.* AU - Conrad, M. AU - Muckenthaler, M.* C1 - 70936 C2 - 55824 TI - Author Correction: Mechanisms controlling cellular and systemic iron homeostasis. JO - Nat. Rev. Mol. Cell Biol. PY - 2024 SN - 1471-0072 ER - TY - JOUR AB - Heterochromatin is a key characteristic of eukaryotic genomes. Since its cytological description nearly 100 years ago, our understanding of heterochromatin features and functions, including transcription repression and genome stability, have continuously evolved. In this Viewpoint article, experts provide their current opinions on heterochromatin definition, types and functional mechanisms. AU - Bell, O.* AU - Burton, A. AU - Dean, C.* AU - Gasser, S.M.* AU - Torres-Padilla, M.E. C1 - 67621 C2 - 53928 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 691-694 TI - Heterochromatin definition and function. JO - Nat. Rev. Mol. Cell Biol. VL - 24 IS - 10 PB - Nature Portfolio PY - 2023 SN - 1471-0072 ER - TY - JOUR AB - Viewing metabolism through the lens of exercise biology has proven an accessible and practical strategy to gain new insights into local and systemic metabolic regulation. Recent methodological developments have advanced understanding of the central role of skeletal muscle in many exercise-associated health benefits and have uncovered the molecular underpinnings driving adaptive responses to training regimens. In this Review, we provide a contemporary view of the metabolic flexibility and functional plasticity of skeletal muscle in response to exercise. First, we provide background on the macrostructure and ultrastructure of skeletal muscle fibres, highlighting the current understanding of sarcomeric networks and mitochondrial subpopulations. Next, we discuss acute exercise skeletal muscle metabolism and the signalling, transcriptional and epigenetic regulation of adaptations to exercise training. We address knowledge gaps throughout and propose future directions for the field. This Review contextualizes recent research of skeletal muscle exercise metabolism, framing further advances and translation into practice. AU - Smith, J.A.B.* AU - Murach, K.A.* AU - Dyar, K.A. AU - Zierath, J.R.* C1 - 67898 C2 - 54376 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 607-632 TI - Exercise metabolism and adaptation in skeletal muscle. JO - Nat. Rev. Mol. Cell Biol. VL - 24 IS - 9 PB - Nature Portfolio PY - 2023 SN - 1471-0072 ER - TY - JOUR AB - The research field of ferroptosis has seen exponential growth over the past few years, since the term was coined in 2012. This unique modality of cell death, driven by iron-dependent phospholipid peroxidation, is regulated by multiple cellular metabolic pathways, including redox homeostasis, iron handling, mitochondrial activity and metabolism of amino acids, lipids and sugars, in addition to various signalling pathways relevant to disease. Numerous organ injuries and degenerative pathologies are driven by ferroptosis. Intriguingly, therapy-resistant cancer cells, particularly those in the mesenchymal state and prone to metastasis, are exquisitely vulnerable to ferroptosis. As such, pharmacological modulation of ferroptosis, via both its induction and its inhibition, holds great potential for the treatment of drug-resistant cancers, ischaemic organ injuries and other degenerative diseases linked to extensive lipid peroxidation. In this Review, we provide a critical analysis of the current molecular mechanisms and regulatory networks of ferroptosis, the potential physiological functions of ferroptosis in tumour suppression and immune surveillance, and its pathological roles, together with a potential for therapeutic targeting. Importantly, as in all rapidly evolving research areas, challenges exist due to misconceptions and inappropriate experimental methods. This Review also aims to address these issues and to provide practical guidelines for enhancing reproducibility and reliability in studies of ferroptosis. Finally, we discuss important concepts and pressing questions that should be the focus of future ferroptosis research. AU - Jiang, X.* AU - Stockwell, B.R.* AU - Conrad, M. C1 - 61133 C2 - 50056 CY - Heidelberger Platz 3, Berlin, 14197, Germany SP - 266-282 TI - Ferroptosis: Mechanisms, biology and role in disease. JO - Nat. Rev. Mol. Cell Biol. VL - 22 IS - 4 PB - Nature Research PY - 2021 SN - 1471-0072 ER - TY - JOUR AU - Götz, M. AU - Huttner, W.B.* C1 - 2752 C2 - 23401 SP - 777-788 TI - The Cell Biology of Neurogenesis. JO - Nat. Rev. Mol. Cell Biol. VL - 6 PY - 2005 SN - 1471-0072 ER -