Biology subjects

Yokota, M.

Publications and source records attributed to Yokota, M..

3 recordsLinked to original sources

bioRxiv2025

Altered laminin signaling destinates melanocyte reprogramming in vitiligo

Vitiligo is an acquired depigmenting skin disorder characterized by progressive melanocyte loss, but the cellular mechanisms driving this process remain unclear. Here, we identify melanocyte dedifferentiation as a central and reversible pathogenic mechanism in vitiligo. In healthy human skin, melanocytes reside within a basement membrane niche defined by dystroglycan-laminin-211 adhesion. In contrast, vitiligo lesions exhibit aberrant extracellular matrix remodeling, leading to an adhesion switch to integrin 3{beta}1-laminin-332 interactions. This shift promotes melanocyte dedifferentiation via Rho-F-actin-dependent activation of Hippo and MAPK pathways, resulting in c-Jun-mediated transcriptional changes. Dedifferentiated melanocytes lose their pigment-producing identity and acquire neural crest-like features with multilineage potential. Importantly, this process is reversible. Pharmacological inhibition of involved pathways restores melanocyte differentiation and induces repigmentation in both vitiligo mouse models and ex vivo patient skin. Notably, JAK inhibitors also promote redifferentiation independently of immune modulation. These findings uncover melanocyte dedifferentiation as a fundamental driver of vitiligo and a tractable therapeutic target, offering new opportunities for therapeutic intervention.

cell biology↗

bioRxiv2022

Identification of a novel chalcone reductase gene for isoliquiritigenin biosynthesis in dahlia (Dahlia variabilis)

Butein is one of flavonoids conferring bright yellow flower color and is a precursor of aurone in some species. Butein is synthesized by two steps, 3-malonyl CoA and 4-coumaloyl CoA are converted to isoliquiritigenin in the first step, and then isoliquiritigenin is converted to butein in the second step. In the first step, chalcone synthase (CHS) and chalcone reductase (CHR) catalyze this reaction, however, CHR has been reported for the isoflavone biosynthesis pathway in legumes, and CHR for butein biosynthesis has not yet been isolated. In this study, we report CHR that is evolutionally different gene from legume species is involved in isoliquiritigenin biosynthesis in dahlia. To isolate CHR gene, we conducted comparative RNA-seq analysis between Shukuhai and its butein-loss lateral mutant Rinka. We found DvCHR showed significant difference in expression levels that encodes an aldo-keto reductase (AKR) 13 family protein, which was phylogenetically different from legume CHRs belonging to AKR4A family. Gene expression levels and genotype of DvCHR were correlated with butein accumulation among various dahlia cultivars. Though single over expression of DvCHR was not able to accumulate isoliquiritigenin in tobacco, co-overexpression of DvCHR with a chalcone glucosyltransferase Am4'CGT and a MYB transcription factor CaMYBA successfully induced isoliquiritigenin accumulation. In addition, DvCHR homologous gene expression was detected from butein or aurone accumulating Coreopsideae species but not from non-butein or non-aurone accumulating Asteraceae species. These results indicated DvCHR functions as chalcone reductase for butein biosynthesis in dahlia, and isoliquiritigenin biosynthesis in Coreopsideae species has been developed independently from legume species.

plant biology↗

bioRxiv2018

Peroxisomes control mitochondrial dynamics and the mitochondrion-dependent pathway of apoptosis

Summary StatementsWe unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial fission-fusion dynamics, mitochondrion-dependent caspase activation, and cellular apoptosis.\n\nAbstractPeroxisomes cooperate with mitochondria in the performance of cellular metabolic functions such as fatty acid oxidation and maintenance of redox homeostasis. Whether peroxisomes also regulate mitochondrial fission-fusion dynamics or mitochondrion-dependent apoptosis has remained unclear, however. We now show that genetic ablation of the peroxins Pex3 or Pex5, which are essential for peroxisome biogenesis, resulted in mitochondrial fragmentation in mouse embryonic fibroblasts (MEFs) in a manner dependent on dynamin-related protein 1 (Drp1). Conversely, treatment with 4-phenylbutyric acid, an inducer of peroxisome proliferation, resulted in mitochondrial elongation in wild-type MEFs, but not in Pex3-deficient MEFs. We further found that peroxisome deficiency increased the levels of cytosolic cytochrome c and caspase activity under basal conditions without inducing apoptosis. It also greatly enhanced etoposide-induced caspase activation and apoptosis, indicative of an enhanced cellular sensitivity to death signals. Together, our data unveil a previously unrecognized role of peroxisomes in the regulation of mitochondrial dynamics and mitochondrion-dependent apoptosis. Given that mutations of peroxin genes are responsible for lethal disorders such as Zellweger syndrome, effects of such mutations on mitochondrion-dependent apoptosis may contribute to disease pathogenesis.

cell biology↗