bims-cemest Biomed News
on Cell metabolism and stress
Issue of 2025–01–19
fifteen papers selected by
Jessica Rosarda, Uniformed Services University
  1. The role of mitochondrial remodeling in neurodegenerative diseases.
  2. Beyond Misfolding: A New Paradigm for the Relationship Between Protein Folding and Aggregation.
  3. Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.
  4. Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.
  5. Dopamine degrades ferritin by chaperone-mediated autophagy to elevate mitochondrial iron level in astroglial cells.
  6. Reductive stress: The key pathway in metabolic disorders induced by overnutrition.
  7. Illuminating the impact of N-terminal acetylation: from protein to physiology.
  8. Interaction and regulation of the mitochondrial proteome - in health and disease.
  9. Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.
  10. Stress signaling caused by mitochondrial import malfunction can be terminated by SIFI: importance of stress response silencing.
  11. Multi-organelle imaging with dye combinations: targeting the ER, mitochondria, and plasma membrane.
  12. eIF4F-mediated Dysregulation of mRNA Translation in Cancer.
  13. Mutations in histones dysregulate copper homeostasis leading to defect in Sec61 dependent protein translocation mechanism in Saccharomyces cerevisiae.
  14. The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes.
  15. Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.
  1. Neurochem Int. 2025 Jan 09. pii: S0197-0186(24)00254-7. [Epub ahead of print]183 105927
    The role of mitochondrial remodeling in neurodegenerative diseases.
    Duanqin Guan, Congmin Liang, Dongyan Zheng, Shizhen Liu, Jiankun Luo, Ziwei Cai, He Zhang, Jialong Chen.
      Neurodegenerative diseases are a group of diseases that pose a serious threat to human health, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS). In recent years, it has been found that mitochondrial remodeling plays an important role in the onset and progression of neurodegenerative diseases. Mitochondrial remodeling refers to the dynamic regulatory process of mitochondrial morphology, number and function, which can affect neuronal cell function and survival by regulating mechanisms such as mitochondrial fusion, division, clearance and biosynthesis. Mitochondrial dysfunction is an important intrinsic cause of the pathogenesis of neurodegenerative diseases. Mitochondrial remodeling abnormalities are involved in energy metabolism in neurodegenerative diseases. Pathological changes in mitochondrial function and morphology, as well as interactions with other organelles, can affect the energy metabolism of dopaminergic neurons and participate in the development of neurodegenerative diseases. Since the number of patients with PD and AD has been increasing year by year in recent years, it is extremely important to take effective interventions to significantly reduce the number of morbidities and to improve people's quality of life. More and more researchers have suggested that mitochondrial remodeling and related dynamics may positively affect neurodegenerative diseases in terms of neuronal and self-adaptation to the surrounding environment. Mitochondrial remodeling mainly involves its own fission and fusion, energy metabolism, changes in channels, mitophagy, and interactions with other cellular organelles. This review will provide a systematic summary of the role of mitochondrial remodeling in neurodegenerative diseases, with the aim of providing new ideas and strategies for further research on the treatment of neurodegenerative diseases.
    Keywords:  Biosynthesis; Mitochondrial quality control; Mitochondrial remodeling; Neurodegenerative diseases
    DOI:  https://doi.org/10.1016/j.neuint.2024.105927
  2. Int J Mol Sci. 2024 Dec 24. pii: 53. [Epub ahead of print]26(1):
    Beyond Misfolding: A New Paradigm for the Relationship Between Protein Folding and Aggregation.
    Seong Il Choi, Yoontae Jin, Yura Choi, Baik L Seong.
      Aggregation is intricately linked to protein folding, necessitating a precise understanding of their relationship. Traditionally, aggregation has been viewed primarily as a sequential consequence of protein folding and misfolding. However, this conventional paradigm is inherently incomplete and can be deeply misleading. Remarkably, it fails to adequately explain how intrinsic and extrinsic factors, such as charges and cellular macromolecules, prevent intermolecular aggregation independently of intramolecular protein folding and structure. The pervasive inconsistencies between protein folding and aggregation call for a new framework. In all combined reactions of molecules, both intramolecular and intermolecular rate (or equilibrium) constants are mutually independent; accordingly, intrinsic and extrinsic factors independently affect both rate constants. This universal principle, when applied to protein folding and aggregation, indicates that they should be treated as two independent yet interconnected processes. Based on this principle, a new framework provides groundbreaking insights into misfolding, Anfinsen's thermodynamic hypothesis, molecular chaperones, intrinsic chaperone-like activities of cellular macromolecules, intermolecular repulsive force-driven aggregation inhibition, proteome solubility maintenance, and proteinopathies. Consequently, this paradigm shift not only refines our current understanding but also offers a more comprehensive view of how aggregation is coupled to protein folding in the complex cellular milieu.
    Keywords:  Anfinsen’s thermodynamic hypothesis; aggregation; charges; excluded volumes; intermolecular repulsive forces; metastability; misfolding; molecular chaperones; protein folding; proteinopathies; proteome solubility
    DOI:  https://doi.org/10.3390/ijms26010053
  3. bioRxiv. 2024 Oct 01. pii: 2024.09.30.615241. [Epub ahead of print]
    Maintenance of neuronal TDP-43 expression requires axonal lysosome transport.
    Veronica H Ryan, Sydney Lawton, Joel F Reyes, James Hawrot, Ashley M Frankenfield, Sahba Seddighi, Daniel M Ramos, Faraz Faghri, Nicholas L Johnson, Jizhong Zou, Martin Kampmann, John Replogle, Hebao Yuan, Kory R Johnson, Dragan Maric, Ling Hao, Mike A Nalls, Michael E Ward.
      TDP-43 mislocalization and pathology occurs across a range of neurodegenerative diseases, but the pathways that modulate TDP-43 in neurons are not well understood. We generated a Halo-TDP-43 knock-in iPSC line and performed a genome-wide CRISPR interference FACS-based screen to identify modifiers of TDP-43 levels in neurons. A meta-analysis of our screen and publicly available screens identified both specific hits and pathways present across multiple screens, the latter likely responsible for generic protein level maintenance. We identified BORC, a complex required for anterograde lysosome transport, as a specific modifier of TDP-43 protein, but not mRNA, levels in neurons. BORC loss led to longer half-life of TDP-43 and other proteins, suggesting lysosome location is required for proper protein turnover. As such, lysosome location and function are crucial for maintaining TDP-43 protein levels in neurons.
    DOI:  https://doi.org/10.1101/2024.09.30.615241
  4. J Biochem Mol Toxicol. 2025 Jan;39(1): e70133
    Oxidative/Nitrosative Stress, Apoptosis, and Redox Signaling: Key Players in Neurodegenerative Diseases.
    Nuray Üremiş, Muhammed Mehdi Üremiş.
      Neurodegenerative diseases are significant health concerns that have a profound impact on the quality and duration of life for millions of individuals. These diseases are characterized by pathological changes in various brain regions, specific genetic mutations associated with the disease, deposits of abnormal proteins, and the degeneration of neurological cells. As neurodegenerative disorders vary in their epidemiological characteristics and vulnerability of neurons, treatment of these diseases is usually aimed at slowing disease progression. The heterogeneity of genetic and environmental factors involved in the process of neurodegeneration makes current treatment methods inadequate. However, the existence of common molecular mechanisms in the pathogenesis of these diseases may allow the development of new targeted therapeutic strategies. Oxidative and nitrosative stress damages membrane components by accumulating ROS and RNS and disrupting redox balance. This process results in the induction of apoptosis, which is important in the pathogenesis of neurodegenerative diseases through oxidative stress. Studies conducted using postmortem human samples, animal models, and cell cultures have demonstrated that oxidative stress, nitrosative stress, and apoptosis are crucial factors in the development of diseases such as Alzheimer's, Parkinson's, Multiple Sclerosis, amyotrophic lateral sclerosis, and Huntington's disease. The excessive production of reactive oxygen and nitrogen species, elevated levels of free radicals, heightened mitochondrial stress, disturbances in energy metabolism, and the oxidation and nitrosylation of cellular macromolecules are recognized as triggers for neuronal cell death. Challenges in managing and treating neurodegenerative diseases require a better understanding of this field at the molecular level. Therefore, this review elaborates on the molecular mechanisms by which oxidative and nitrosative stress are involved in neuronal apoptosis.
    Keywords:  Oxidative stress; apoptosis; molecular mechanisms; neurodegenerative diseases; nitrosative stress; redox signaling
    DOI:  https://doi.org/10.1002/jbt.70133
  5. Free Radic Biol Med. 2025 Jan 14. pii: S0891-5849(25)00021-8. [Epub ahead of print]
    Dopamine degrades ferritin by chaperone-mediated autophagy to elevate mitochondrial iron level in astroglial cells.
    Som Dev, Somya Asthana, Pratibha Singh, Pankaj Seth, Chayanika Banerjee, Chinmay K Mukhopadhyay.
      Iron accumulation and mitochondrial dysfunction in astroglia are reported in Parkinson's disease (PD). Astroglia control iron availability in neurons in which dopamine (DA) synthesis is affected in PD. Despite their intimate relationship the role of DA in astroglial iron homeostasis is limited. Here we show that DA degrades iron storage protein ferritin in astroglial cells involving lysosomal proteolysis. Lysosomal ferritinophagy is mainly associated with macroautophagy; however, we revealed the involvement of chaperone-mediated autophagy (CMA) in DA-induced ferritin degradation. In CMA, cytosolic proteins containing a specific pentapeptide motif bind with HSC70 to be transported to lysosome mediated by LAMP2A. We identified the conserved pentapeptide motif in ferritin-H (Ft-H), mutations of which resulted loss of its interaction with HSC70. Pharmacological inhibitors of HSC70 or LAMP2/2A knockdown blocks DA-induced Ft-H degradation. DA also induces cytosolic cargo NCOA4 for ferritinophagy. We further reveal that DA promotes cathepsin B to lysis ferritin within the lysosome. Inhibitor of cathepsin B, knocking down of LAMP2, or HSC70 inhibitor attenuate DA-induced elevated mitochondrial iron level. Our results establish a direct role of DA on astroglial iron homeostasis and novel involvement of CMA in ferritin degradation in response to a biological stimulus. These results also may help in better understanding iron dyshomeostasis and mitochondrial dysfunction reported in PD.
    Keywords:  Dopamine; NCOA4; astroglia; cathepsin B; chaperone-mediated autophagy; ferritin; mitochondrial iron
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2025.01.021
  6. J Adv Res. 2025 Jan 11. pii: S2090-1232(25)00031-1. [Epub ahead of print]
    Reductive stress: The key pathway in metabolic disorders induced by overnutrition.
    Shiyi Zhang, Na Wang, Zhichao Gao, Jia Gao, Xiaohui Wang, Hao Xie, Cong-Yi Wang, Shu Zhang.
       BACKGROUND: The balance of redox states is crucial for maintaining physiological homeostasis. For decades, the focus has been mainly on the concept of oxidative stress, which is involved in the mechanism of almost all diseases. However, robust evidence has highlighted that reductive stress, the other side of the redox spectrum, plays a pivotal role in the development of various diseases, particularly those related to metabolism and cardiovascular health.
    AIM OF REVIEW: In this review, we present an extensive array of evidence for the occurrence of reductive stress and its significant implications mainly in metabolic and cardiovascular diseases.
    KEY SCIENTIFIC CONCEPTS OF REVIEW: Reductive stress is defined as a shift in the cellular redox balance towards a more reduced state, characterized by an excess of endogenous reductants (such as NADH, NADPH, and GSH) over their oxidized counterparts (NAD+, NADP+, and GSSG). While oxidative stress has been the predominant mechanism studied in obesity, metabolic disorders, and cardiovascular diseases, growing evidence underscores the critical role of reductive stress. This review discusses how reductive stress contributes to metabolic and cardiovascular pathologies, emphasizing its effects on key cellular processes. For example, excessive NADH accumulation can disrupt mitochondrial function by impairing the electron transport chain, leading to decreased ATP production and increased production of reactive oxygen species. In the endoplasmic reticulum (ER), an excess of reductive equivalents hampers protein folding, triggering ER stress and activating the unfolded protein response, which can lead to insulin resistance and compromised cellular homeostasis. Furthermore, we explore how excessive antioxidant supplementation can exacerbate reductive stress by further shifting the redox balance, potentially undermining the beneficial effects of exercise, impairing cardiovascular health, and aggravating metabolic disorders, particularly in obese individuals. This growing body of evidence calls for a reevaluation of the role of reductive stress in disease pathogenesis and therapeutic interventions.
    Keywords:  Antioxidants; Cardiovascular diseases; Endoplasmic reticulum stress; Metabolic disorders; Mitochondrial dysfunction; Reductive stress
    DOI:  https://doi.org/10.1016/j.jare.2025.01.012
  7. Nat Commun. 2025 Jan 15. 16(1): 703
    Illuminating the impact of N-terminal acetylation: from protein to physiology.
    Nina McTiernan, Ine Kjosås, Thomas Arnesen.
      N-terminal acetylation is a highly abundant protein modification in eukaryotic cells. This modification is catalysed by N-terminal acetyltransferases acting co- or post-translationally. Here, we review the eukaryotic N-terminal acetylation machinery: the enzymes involved and their substrate specificities. We also provide an overview of the impact of N-terminal acetylation, including its effects on protein folding, subcellular targeting, protein complex formation, and protein turnover. In particular, there may be competition between N-terminal acetyltransferases and other enzymes in defining protein fate. At the organismal level, N-terminal acetylation is highly influential, and its impairment was recently linked to cardiac dysfunction and neurodegenerative diseases.
    DOI:  https://doi.org/10.1038/s41467-025-55960-5
  8. Expert Rev Proteomics. 2025 Jan 15. 1-15
    Interaction and regulation of the mitochondrial proteome - in health and disease.
    Johan Palmfeldt.
       INTRODUCTION: Mitochondria contain multiple pathways including energy metabolism and several signaling and synthetic pathways. Mitochondrial proteomics is highly valuable for studying diseases including inherited metabolic disorders, complex and common disorders like neurodegeneration, diabetes, and cancer, since they all to some degree have mitochondrial underpinnings.
    AREAS COVERED: The main mitochondrial functions and pathways are outlined, and systematic protein lists are presented. The main energy metabolic pathways are as follows: iron-sulfur cluster synthesis, one carbon metabolism, catabolism of hydrogen sulfide, kynurenines and reactive oxygen species (ROS), and others, described with the aim of laying a foundation for systematic mitochondrial pathway analysis based on proteomics data. The links of the proteins and pathways to functional effects and diseases are discussed. The disease examples are focussed on inherited metabolic disorders, cancer, neurological, and cardiovascular disorders.
    EXPERT OPINION: To elucidate the role of mitochondria in health and disease, there is a need for comprehensive proteomics analyses with stringent, systematic data treatment for proper interpretation of mitochondrial pathway data. In that way, comprehensive hypothesis-based research can be performed based on proteomics data.
    Keywords:  Mitochondrion; NAD; biomarker panels; kynurenine; metabolic disorders; oxidative phosphorylation; proteomics; stress response
    DOI:  https://doi.org/10.1080/14789450.2025.2451704
  9. Mol Ther. 2025 Jan 10. pii: S1525-0016(25)00008-5. [Epub ahead of print]
    Artificial enforcement of the unfolded protein response (UPR) reduces disease features in multiple preclinical models of ALS/FTD.
    Vicente Valenzuela, Daniela Becerra, José I Astorga, Matías Fuentealba, Guillermo Diaz, Leslie Bargsted, Carlos Chacón, Alexis Martinez, Romina Gozalvo, Kasey Jackson, Vania Morales, Macarena Las Heras, Giovanni Tamburini, Leonard Petrucelli, Pablo Sardi, Lars Plate, Claudio Hetz.
      Amyotrophic lateral sclerosis (ALS) and fronto-temporal dementia (FTD) are part of a spectrum of diseases that share several causative genes, resulting in a combinatory of motor and cognitive symptoms and abnormal protein aggregation. Multiple unbiased studies have revealed that proteostasis impairment at the level of the endoplasmic reticulum (ER) is a transversal pathogenic feature of ALS/FTD. The transcription factor XBP1s is a master regulator of the unfolded protein response (UPR), the main adaptive pathway to cope with ER stress. Here we provide evidence of suboptimal activation of the UPR in ALS/FTD models under experimental ER stress. To artificially engage the UPR, we intracerebroventricularly administrated adeno-associated viruses (AAV) to express the active form of XBP1 (XBP1s) in the nervous system of ALS/FTD models. XBP1s expression improved motor performance and extended life span of mutant SOD1 mice, associated with reduced protein aggregation. AAV-XBP1s administration also attenuated disease progression in models of TDP-43 and C9orf72 pathogenesis. Proteomic profiling of spinal cord tissue revealed that XBP1s overexpression improved proteostasis and modulated the expression of a cluster of synaptic and cell morphology proteins. Our results suggest that strategies to improve ER proteostasis may serve as a pan-therapeutic strategy to treat ALS/FTD.
    DOI:  https://doi.org/10.1016/j.ymthe.2025.01.004
  10. Neural Regen Res. 2025 Jan 13.
    Stress signaling caused by mitochondrial import malfunction can be terminated by SIFI: importance of stress response silencing.
    Grace Hohman, Michael Shahid, Mohamed A Eldeeb.
      
    DOI:  https://doi.org/10.4103/NRR.NRR-D-24-01169
  11. J Mater Chem B. 2025 Jan 16.
    Multi-organelle imaging with dye combinations: targeting the ER, mitochondria, and plasma membrane.
    Yogesh Dubey, Sriram Kanvah.
      Multi-organelle imaging allows the visualization of multiple organelles within a single cell, allowing monitoring of the cellular processes in real-time using various fluorescent probes that target specific organelles. However, the limited availability of fluorophores and potential spectral overlap present challenges, and many optimized designs are still in nascency. In this work, we synthesized various sulfonamide-based organic fluorophores that emit in the blue, green, and red regions to target different sub-cellular organelles. By utilizing binary mixtures, we successfully demonstrated multiple imaging of the sub-cellular organelles, such as the endoplasmic reticulum, plasma membrane, and mitochondria in HeLa cells, and dual imaging of the endoplasmic reticulum and mitochondria in A549 lung carcinoma cells with the help of blue and red-emitting fluorophores without any spectral spillover. Additionally, these photostable probes allowed precise cell staining and differentiation, structural features, and live cell dynamics. This approach of utilizing fluorescent mixtures can gain traction for various cellular studies and investigations.
    DOI:  https://doi.org/10.1039/d4tb02456g
  12. RNA. 2025 Jan 14. pii: rna.080340.124. [Epub ahead of print]
    eIF4F-mediated Dysregulation of mRNA Translation in Cancer.
    Mehdi Amiri, Niaz Mahmood, Soroush Tahmasebi, Nahum Sonenberg.
      Messenger RNA (mRNA) translational control plays a pivotal role in regulating cellular proteostasis under physiological and pathological conditions. Dysregulated mRNA translation is pervasive in cancer, in which protein synthesis is elevated to support accelerated cell growth and proliferation. Consequently, targeting the mRNA translation machinery has emerged as a therapeutic strategy to treat cancer. In this perspective, we summarize the current knowledge of translation dysregulation in cancer, with emphasis on the eukaryotic translation initiation factor 4F (eIF4F) complex. We outline recent endeavors to apply this knowledge to develop novel treatment strategies to combat cancer.
    Keywords:  eIF4A; eIF4E; eIF4F; eIF4G; mTOR
    DOI:  https://doi.org/10.1261/rna.080340.124
  13. J Biol Chem. 2025 Jan 08. pii: S0021-9258(25)00010-9. [Epub ahead of print] 108163
    Mutations in histones dysregulate copper homeostasis leading to defect in Sec61 dependent protein translocation mechanism in Saccharomyces cerevisiae.
    Santoshi Acharjee, Rajshree Pal, Smriti Anand, Prateeksha Thakur, Vandana Anjana, Ranu Singh, Mrittika Paul, Ashis Biswas, Raghuvir Singh Tomar.
      The translocation of proteins from the cytoplasm to the endoplasmic reticulum occurs via a conserved Sec61 protein channel. Previously, we reported that mutations in histones cause downregulation of a CUP1 copper metallothionein and copper exposure inhibits the activity of Sec61. However, the role of epigenetic dysregulation on the activity of channel is not clear. Identification of cellular factors regulating copper metabolism and Sec61 activity is needed as the dysregulation can cause human diseases. In this study, we elucidate the intricate relationship between copper homeostasis and Sec61-mediated protein translocation. Utilizing copper-sensitive yeast histone mutants exhibiting deficiencies in the expression of CUP1, we uncover a copper-specific impairment of the protein translocation process, causing a reduction in the maturation of secretory proteins. Our findings highlight the inhibitory effect of copper on both co-translational and post-translational protein translocations. We demonstrate that supplementation with a copper-specific chelator, or amino acids such as cysteine, histidine, and reduced glutathione, zinc and overexpression of CUP1 restores the translocation process and growth. This study, for the first time provides a functional insight on epigenetic and metabolic regulation of copper homeostasis in governing Sec61-dependent protein translocation process and may be useful to understand human disorders of copper metabolism.
    Keywords:  Sec61; copper homeostasis; endoplasmic reticulum; protein translocation
    DOI:  https://doi.org/10.1016/j.jbc.2025.108163
  14. Nat Metab. 2025 Jan 10.
    The pentose phosphate pathway controls oxidative protein folding and prevents ferroptosis in chondrocytes.
    Shauni Loopmans, Katerina Rohlenova, Thomas van Brussel, Ingrid Stockmans, Karen Moermans, Nicolas Peredo, Peter Carmeliet, Diether Lambrechts, Steve Stegen, Geert Carmeliet.
      Bone lengthening and fracture repair depend on the anabolic properties of chondrocytes that function in an avascular milieu. The limited supply of oxygen and nutrients calls into question how biosynthesis and redox homeostasis are guaranteed. Here we show that glucose metabolism by the pentose phosphate pathway (PPP) is essential for endochondral ossification. Loss of glucose-6-phosphate dehydrogenase in chondrocytes does not affect cell proliferation because reversal of the non-oxidative PPP produces ribose-5-phosphate. However, the decreased NADPH production reduces glutathione recycling, resulting in decreased protection against the reactive oxygen species (ROS) produced during oxidative protein folding. The disturbed proteostasis activates the unfolded protein response and protein degradation. Moreover, the oxidative stress induces ferroptosis, which, together with altered matrix properties, results in a chondrodysplasia phenotype. Collectively, these data show that in hypoxia, the PPP is crucial to produce reducing power that confines ROS generated by oxidative protein folding and thereby controls proteostasis and prevents ferroptosis.
    DOI:  https://doi.org/10.1038/s42255-024-01187-5
  15. J Dermatol Sci. 2025 Jan 08. pii: S0923-1811(25)00001-5. [Epub ahead of print]
    Unfolded protein response modulates Tyrosinase levels and melanin production during melanogenesis.
    Akari Yamazaki, Issei Omura, Yasunao Kamikawa, Michihiro Hide, Akio Tanaka, Masayuki Kaneko, Kazunori Imaizumi, Atsushi Saito.
       BACKGROUND: Melanocytes protect the body from ultraviolet radiation by synthesizing melanin. Tyrosinase, a key enzyme in melanin production, accumulates in the endoplasmic reticulum (ER) during melanin synthesis, potentially causing ER stress. However, regulating ER function for melanin synthesis has been less studied than controlling Tyrosinase activity.
    OBJECTIVE: This study investigates the regulatory mechanisms of melanin production, focusing on ER stress and the ER stress-induced response.
    METHODS: B16 mouse melanoma cells induced to undergo melanogenesis were treated with unfolded protein response (UPR) inhibitors or chemical chaperones, and their effects on melanogenesis were analyzed.
    RESULTS: During melanogenesis in B16 cells stimulated by alpha-melanocyte-stimulating hormone (α-MSH), ER stress and UPR activation occurred, accompanied by increased Tyrosinase protein. Reducing IRE1 and ATF6 branch activity lowered melanin levels, while chemical chaperone treatment restored melanin production and increased Tyrosinase levels.
    CONCLUSION: UPR activation, linked to elevated Tyrosinase levels, influences melanin production during melanogenesis. Modulating UPR can regulate melanin synthesis and provides a potential new approach for treating pigmentation disorders.
    Keywords:  Endoplasmic reticulum stress; Melanin production; Pigmentation disorders; Tyrosinase; Unfolded protein response
    DOI:  https://doi.org/10.1016/j.jdermsci.2025.01.001
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