The initial phase of peroxisomal fission requires the peroxisomal membrane protein Peroxin 11 (Pex11p), which remodels the membrane, resulting in organelle elongation. Here, we identify an additional function for Pex11p, demonstrating that Pex11p also plays a crucial role in the final step of peroxisomal fission: dynamin-like protein (DLP)-mediated membrane scission. First, we demonstrate that yeast Pex11p is necessary for the function of the GTPase Dynamin-related 1 (Dnm1p) in vivo. In addition, our data indicate that Pex11p physically interacts with Dnm1p and that inhibiting this interaction compromises peroxisomal fission. Finally, we demonstrate that Pex11p functions as a GTPase activating protein (GAP) for Dnm1p in vitro. Similar observations were made for mammalian Pex11β and the corresponding DLP Drp1, indicating that DLP activation by Pex11p is conserved. Our work identifies a previously unknown requirement for a GAP in DLP function.
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http://dx.doi.org/10.1073/pnas.1418736112 | DOI Listing |
Mitochondrion
January 2025
Organelle Biology and Cellular Ageing Lab, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India. Electronic address:
Mitochondrial morphology is a result of regulated opposite events called fission and fusion and requires the GTPase, dynamin-related protein 1 (DRP1/Dnm1), or its homologs. A recent clinical report identified a heterozygous missense mutation in the human DRP1 that replaces Glycine (G) 149 with Arginine (R) and results in debilitating conditions in the patient. In this study, we mimicked this mutation in yeast Dnm1 (G178R) and investigated the impact of the pathogenic mutation on the protein's function.
View Article and Find Full Text PDFJ Physiol Biochem
December 2024
Department of Exercise Physiology, Faculty of Sport Sciences, Shahid Rajaee Teacher Training University, Tehran, Iran.
The circadian clock regulates mitochondrial function and affects time-dependent metabolic responses to exercise. The present study aimed to determine the effects of aerobic exercise timing at the light-dark phase on the proteins expression of the circadian clock, mitochondrial dynamics, and, NAD-SIRT1-PPARα axis in skeletal muscle of high-fat diet-induced diabetic mice. In this experimental study, thirty male mice were randomly assigned into two groups based on time: the early light phase, ZT3, and the early dark phase, ZT15, and three groups at each time: (1) Healthy Control (HC), (2) Diabetic Control (DC), and (3) Diabetic + Exercise (DE).
View Article and Find Full Text PDFSci Rep
December 2024
Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Center, University of Freiburg, Breisacherstr. 62, 79106, Freiburg, Germany.
Mutations in the mitochondrial enzyme propionyl-CoA carboxylase (PCC) cause propionic aciduria (PA). Chronic kidney disease (CKD) is a known long-term complication. However, good metabolic control and standard therapy fail to prevent CKD.
View Article and Find Full Text PDFInt J Biol Macromol
December 2024
College of Animal Science and Technology, Northeast Agricultural University, Harbin, Heilongjiang 150030, China. Electronic address:
Konjac glucomannan (KGM) and κ-carrageenan are polysaccharides that have garnered attention for their potential health benefits. This study aimed to evaluate the maternal supplementation of KGM and κ-carrageenan (SF) during later gestation and lactation on the effect of hepatic lipid metabolism and colonic microflora in offspring. Regarding antioxidant and inflammatory factors in the suckling piglet liver, our results showed that nuclear factor erythroid 2-related factor 2 (Nrf2) and interleukin (IL)-10 levels were significantly increased in the SF group (P < 0.
View Article and Find Full Text PDFInt J Mol Med
February 2025
NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien‑I Memorial Hospital and Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, P.R. China.
Traditional Chinese Medicine (TCM) has demonstrated promising efficacy in managing and preventing the early‑stage diabetic nephropathy (DN). Although the exact mechanisms remain elusive, clinical evidence has suggested that Jinlida granules (JLD) are beneficial in improving renal function among patients with DN. The present study aimed to elucidate the effect of JLD on DN and the underlying molecular mechanism.
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