Peroxisome biogenesis involves two pathways: growth and division from pre-existing mature peroxisomes and de novo biogenesis from the endoplasmic reticulum, with a contribution from mitochondria, particularly in human peroxisome-deficient cells. However, the essential components that control peroxisome de novo biogenesis are largely unknown. Dual organelle localized ubiquitin ligase MARCH5 functions on peroxisomes to control pexophagy. Here, we show that mitochondria-localized MARCH5 is essential for the formation of vesicles in the de novo biogenesis of peroxisomes from mitochondria in human cell lines. Loss of MARCH5 specifically impedes the budding of PEX3-containing vesicles from mitochondria, thereby blocking the formation of pre-peroxisomes. Overall, our study highlights the function of MARCH5 for mitochondria-derived pre-peroxisomes, emphasizing MARCH5 as one regulator to maintain peroxisome homeostasis.
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http://dx.doi.org/10.1016/j.devcel.2024.09.029 | DOI Listing |
J Cell Biol
February 2025
Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.
Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite for its subsequent fusion with endolysosomal organelles and degradation of the sequestered cargo. ATG9A, a key integral membrane protein of the autophagy pathway, is best known for its role in the formation and expansion of phagophores.
View Article and Find Full Text PDFClin Epigenetics
December 2024
Hereditary Cancer Group, ONCOBELL Program, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Spain.
Background: Lynch syndrome (LS), characterised by an increased risk for cancer, is mainly caused by germline pathogenic variants affecting a mismatch repair gene (MLH1, MSH2, MSH6, PMS2). Occasionally, LS may be caused by constitutional MLH1 epimutation (CME) characterised by soma-wide methylation of one allele of the MLH1 promoter. Most of these are "primary" epimutations, arising de novo without any apparent underlying cis-genetic cause, and are reversible between generations.
View Article and Find Full Text PDFPlant Physiol
December 2024
Department of Biology, BNL 463, 50 Bell Ave, Upton NY 11973, USA.
In eukaryotes, Target of Rapamycin (TOR), a conserved protein sensor kinase, integrates diverse environmental cues, including growth factor signals, energy availability, and nutritional status, to direct cell growth. In plants, TOR is activated by light and sugars and regulates a wide range of cellular processes, including protein synthesis and metabolism. Fatty acid synthesis is key to membrane biogenesis that is required for cell growth.
View Article and Find Full Text PDFNeurotherapeutics
December 2024
Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX, 77030, USA; Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA; Department of Cardiology, Houston Methodist DeBakey Heart and Vascular Center, Houston Methodist Hospital, Houston, TX, 77030, USA. Electronic address:
Mitochondrial dysfunction is an important driver of neurodegeneration and synaptic abnormalities in Alzheimer's disease (AD). Amyloid beta (Aβ) in mitochondria leads to increased reactive oxygen species (ROS) production, resulting in a vicious cycle of oxidative stress in coordination with a defective electron transport chain (ETC), decreasing ATP production. AD neurons exhibit impaired mitochondrial dynamics, evidenced by fusion and fission imbalances, increased fragmentation, and deficient mitochondrial biogenesis, contributing to fewer mitochondria in brains of AD patients.
View Article and Find Full Text PDFMol Biol Evol
December 2024
State Key Laboratory of Systematic and Evolutionary Botany, Institute of Botany, Chinese Academy of Sciences, Beijing 100093, China.
The origin of genes from non-coding sequences is a long-term and fundamental biological question. However, how de novo genes originate and integrate into the existing pathways to regulate phenotypic variations is largely unknown. Here, we selected seven genes from 782 de novo genes for functional exploration based on transcriptional and translational evidence.
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