Álvarez-Sánchez Melisa, Ramírez-Noguez Matías, Aguirre-López Beatriz, Peraza-Reyes Leonardo
Departamento de Bioquímica y Biología Estructural, Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico City, Mexico.
Microb Cell. 2025 Sep 12;12:255-273. doi: 10.15698/mic2025.09.860. eCollection 2025.
Eucaryotic cell functioning and development depend on the concerted activity of its organelles. In the model fungus , sexual development involves a dynamic regulation of mitochondria, peroxisomes and the endoplasmic reticulum (ER), suggesting that their activity during this process is coordinated. The ER-Mitochondria Encounter Structure (ERMES) is a tether complex composed of the ER protein Mmm1 and the mitochondrial proteins Mdm10, Mdm12 and Mdm34, which mediates membrane contact-site formation between these organelles. This complex also mediates interactions between mitochondria and peroxisomes. Here we analyzed the role of the ERMES complex during development. By studying a thermosensitive mutant, we show that MDM10 is required for mitochondrial morphology and distribution, as well as for peroxisome membrane-remodeling and motility. We discovered that lipid droplets exhibit a subapical hyphal localization, which depends on MDM10. MDM10 is also required for ER shaping and dynamics, notably of the apical ER domains of the polarized-growing hyphal region, in a process that involves the activity of the protein YOP1. We also show that apical ER shaping involves a Spitzenkörper-associated membrane traffic, which implicates MDM10, and that the mycelial growth defect of mutants is exacerbated when the ER-shaping proteins YOP1 or RTN1 are loss. Finaly, we show that MMM1 is strictly required for mycelial growth and sexual development, suggesting that its activity is essential. Our results show that the activity of distinct organelles depends on the ERMES complex, and that the function of this complex is critical for growth and development.
真核细胞的功能和发育依赖于其细胞器的协同活动。在模式真菌中，有性发育涉及线粒体、过氧化物酶体和内质网（ER）的动态调节，这表明它们在此过程中的活动是协调的。内质网-线粒体接触结构（ERMES）是一种由内质网蛋白Mmm1和线粒体蛋白Mdm10、Mdm12和Mdm34组成的系链复合物，它介导这些细胞器之间的膜接触位点形成。该复合物还介导线粒体与过氧化物酶体之间的相互作用。在这里，我们分析了ERMES复合物在发育过程中的作用。通过研究一个温度敏感突变体，我们发现MDM10对于线粒体的形态和分布，以及过氧化物酶体膜重塑和运动性是必需的。我们发现脂滴呈现亚顶端菌丝定位，这依赖于MDM10。MDM10对于内质网的形态和动态变化也是必需的，特别是在极化生长的菌丝区域的顶端内质网结构域，这一过程涉及蛋白YOP1的活性。我们还表明顶端内质网形态形成涉及与Spitzenkörper相关的膜运输，这与MDM10有关，并且当内质网形态形成蛋白YOP1或RTN1缺失时，突变体的菌丝生长缺陷会加剧。最后，我们表明MMM1对于菌丝生长和有性发育是严格必需的，这表明其活性至关重要。我们的结果表明，不同细胞器的活动依赖于ERMES复合物，并且该复合物的功能对于生长和发育至关重要。
