Plasticity and structural alterations of mitochondria and sarcoplasmic organelles in muscles of mice deficient in α-dystrobrevin, a component of the dystrophin-glycoprotein complex DOI

Saad O Malik,

Alissa Wierenga,

Chenlang Gao

et al.

Human Molecular Genetics, Journal Year: 2024, Volume and Issue: 33(13), P. 1107 - 1119

Published: March 20, 2024

The dystrophin-glycoprotein complex (DGC) plays a crucial role in maintaining the structural integrity of plasma membrane and neuromuscular junction. In this study, we investigated impact deficiency α-dystrobrevin (αdbn), component DGC, on homeostasis intracellular organelles, specifically mitochondria sarcoplasmic reticulum (SR). αdbn deficient muscles, observed significant increase membrane-bound ATP synthase levels, marker for oxidative muscle fiber types compared to wild-type. Furthermore, examination fibers using electron microscopy revealed profound alterations organization SR within certain myofibrils fibers. This included formation hyper-branched intermyofibrillar with extended connections, an extensive network spanning several myofibrils, substantial number/density subsarcolemmal mitochondria. Concurrently, some cases, mitochondria, such as cristae loss, fragmentation, swelling, vacuoles inclusions mitochondrial matrix cristae. Muscles also displayed notable morphology SR, along distinct anomalous concentric structures known whorls. These whorls were prevalent αdbn-deficient mice but absent wild-type muscles. results suggest DGC regulating particularly cells. remodeling may represent novel mechanism unfolded protein response (UPR)

Language: Английский

Lipid droplet biogenesis and functions in health and disease DOI Open Access

Armella Zadoorian,

Ximing Du, Hongyuan Yang

et al.

Nature Reviews Endocrinology, Journal Year: 2023, Volume and Issue: 19(8), P. 443 - 459

Published: May 23, 2023

Language: Английский

Citations

256
SGLT2 inhibitors: role in protective reprogramming of cardiac nutrient transport and metabolism DOI Open Access
Milton Packer

Nature Reviews Cardiology, Journal Year: 2023, Volume and Issue: 20(7), P. 443 - 462

Published: Jan. 6, 2023

Language: Английский

Citations

102
Mitochondrial signalling and homeostasis: from cell biology to neurological disease DOI Creative Commons
Jack J. Collier, Monika Oláhová, Thomas G. McWilliams

et al.

Trends in Neurosciences, Journal Year: 2023, Volume and Issue: 46(2), P. 137 - 152

Published: Jan. 10, 2023

Efforts to understand how mitochondrial dysfunction contributes neurodegeneration have primarily focussed on the role of mitochondria in neuronal energy metabolism. However, progress understanding etiological nature emerging functions has yielded new ideas about basis neurological disease. Studies aimed at deciphering signal through interorganellar contacts, vesicular trafficking, and metabolic transmission revealed that regulation immunometabolism, cell death, organelle dynamics, neuroimmune interplay are critical determinants neural health. Moreover, homeostatic mechanisms exist protect health turnover via nanoscale proteostasis lysosomal degradation become integrated within signalling pathways support plasticity stress responses nervous system. This review highlights these distinct converge influence contribute disease pathology.

Language: Английский

Citations

72
Lipid droplets and polyunsaturated fatty acid trafficking: Balancing life and death DOI Creative Commons
Mauro Danielli,

Leja Perne,

Eva Jarc

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2023, Volume and Issue: 11

Published: Jan. 27, 2023

Lipid droplets are fat storage organelles ubiquitously distributed across the eukaryotic kingdom. They have a central role in regulating lipid metabolism and undergo dynamic turnover of biogenesis breakdown to meet cellular requirements for fatty acids, including polyunsaturated acids. Polyunsaturated acids esterified membrane phospholipids define fluidity can be released by activity phospholipases A

Language: Английский

Citations

69
Coronaviral ORF6 protein mediates inter‐organelle contacts and modulates host cell lipid flux for virus production DOI Open Access

Mengzhen Yue,

Bing Hu, Jiajia Li

et al.

The EMBO Journal, Journal Year: 2023, Volume and Issue: 42(13)

Published: May 23, 2023

Abstract Lipid droplets (LDs) form inter‐organelle contacts with the endoplasmic reticulum (ER) that promote their biogenesis, while LD mitochondria enhance β‐oxidation of contained fatty acids. Viruses have been shown to take advantage lipid viral production, but it remains unclear whether they also modulate interactions between LDs and other organelles. Here, we showed coronavirus ORF6 protein targets is localized mitochondria‐LD ER‐LD contact sites, where regulates biogenesis lipolysis. At molecular level, find inserts into monolayer via its two amphipathic helices. further interacts ER membrane proteins BAP31 USE1 mediate ER‐LDs formation. Additionally, SAM complex in mitochondrial outer link LDs. In doing so, promotes cellular lipolysis reprogram host cell flux facilitate production.

Language: Английский

Citations

26
Role of Perilipins in Oxidative Stress—Implications for Cardiovascular Disease DOI Creative Commons
Mathieu Cinato, Linda Andersson, Azra Miljanovic

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(2), P. 209 - 209

Published: Feb. 7, 2024

Oxidative stress is the imbalance between production of reactive oxygen species (ROS) and antioxidants in a cell. In heart, oxidative may deteriorate calcium handling, cause arrhythmia, enhance maladaptive cardiac remodeling by induction hypertrophic apoptotic signaling pathways. Consequently, dysregulated ROS have been implicated numerous diseases, including heart failure, ischemia–reperfusion injury, hypertrophy, diabetic cardiomyopathy. Lipid droplets (LDs) are conserved intracellular organelles that enable safe stable storage neutral lipids within cytosol. LDs coated with proteins, perilipins (Plins) being one most abundant. this review, we will discuss interplay Plins. Indeed, Plins increasingly recognized for playing critical role beyond energy metabolism lipid handling. Numerous reports suggest an essential purpose LD biogenesis to alleviate cellular stress, such as stress. Given yet unmet suitability targets intervention cardiovascular disease, endogenous antioxidant capacity be beneficial.

Language: Английский

Citations

12
Longitudinal autophagy profiling of the mammalian brain reveals sustained mitophagy throughout healthy aging DOI Creative Commons
Anna Rappe, Helena Vihinen, Fumi Suomi

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 4, 2024

Abstract Mitophagy neutralizes mitochondrial damage, thereby preventing cellular dysfunction and apoptosis. Defects in mitophagy have been strongly implicated age-related neurodegenerative disorders such as Parkinson’s Alzheimer’s disease. While decreases throughout the lifespan of short-lived model organisms, it remains unknown whether a decline occurs aging mammalian brain—a question fundamental importance for understanding cell type- region-specific susceptibility to neurodegeneration. Here, we define longitudinal dynamics basal macroautophagy across neuronal non-neuronal types within intact mouse brain vivo. Quantitative profiling reporter cohorts from young geriatric ages reveals cell- tissue-specific alterations between distinct subregions populations, including dopaminergic neurons, cerebellar Purkinje cells, astrocytes, microglia interneurons. We also find that healthy is hallmarked by dynamic accumulation differentially acidified lysosomes several neural subsets. Our findings argue against any widespread mitophagic activity, instead demonstrating fluctuations trajectory, with strong implications ongoing theragnostic development.

Language: Английский

Citations

9
DGAT1 activity synchronises with mitophagy to protect cells from metabolic rewiring by iron depletion DOI Creative Commons
Maeve Long, Álvaro Sánchez-Martínez,

Marianna Longo

et al.

The EMBO Journal, Journal Year: 2022, Volume and Issue: 41(10)

Published: April 12, 2022

Mitophagy removes defective mitochondria via lysosomal elimination. Increased mitophagy coincides with metabolic reprogramming, yet it remains unknown whether is a cause or consequence of such state changes. The signalling pathways that integrate to sustain cell and tissue integrity also remain poorly defined. We performed temporal metabolomics on mammalian cells treated deferiprone, therapeutic iron chelator stimulates PINK1/PARKIN-independent mitophagy. Iron depletion profoundly rewired the metabolome, hallmarked by remodelling lipid metabolism within minutes treatment. DGAT1-dependent droplet biosynthesis occurred several hours before mitochondrial clearance, droplets bordering upon chelation. demonstrate DGAT1 inhibition restricts in vitro, impaired homeostasis viability. Importantly, genetic vivo significantly neuronal locomotor function Drosophila. Our data define as potent signal rapidly reshapes establishes an unexpected synergy between safeguards integrity.

Language: Английский

Citations

33
BCAA metabolism in pancreatic cancer affects lipid balance by regulating fatty acid import into mitochondria DOI Creative Commons
Klára Gotvaldová, Jitka Špačková, Jiří Novotný

et al.

Cancer & Metabolism, Journal Year: 2024, Volume and Issue: 12(1)

Published: March 26, 2024

Abstract Background Pancreatic ductal adenocarcinoma (PDAC) has been associated with the host dysmetabolism of branched-chain amino acids (BCAAs), however, implications for role BCAA metabolism in PDAC development or progression are not clear. The mitochondrial catabolism valine, leucine, and isoleucine is a multistep process leading to production short-chain R-CoA species. They can be subsequently exported from mitochondria as carnitines (SC-CARs), utilized anabolic pathways, released cells. Methods We examined specificities cellular adaptation strategies starvation cells vitro. used metabolomics lipidomics quantify major metabolic changes response withdrawal. Using confocal microscopy flow cytometry we quantified fluorescence BODIPY probe level lipid droplets (LDs). BODIPY-conjugated palmitate evaluate transport fatty (FAs) into mitochondria. Also, have developed protocol quantification SC-CARs, BCAA-derived metabolites. Results profiling, found that leads massive triglyceride (TG) synthesis LD accumulation. This was suppression activated FA matrix. import rescued inhibitor acetyl-CoA carboxylase (ACC) activator AMP kinase (AMPK), which both regulate carnitine palmitoyltransferase 1A (CPT1) activation status. Conclusions Our data suggest required long chain (LC-CARs) mitochondria, whereas disruption this link results redirection FAs TG its deposition LDs. propose mechanism protects against overload LC-CARs it might part universal reaction acid perturbations during cancer growth, regulating handling storage.

Language: Английский

Citations

8
RNF31 alleviates liver steatosis by promoting p53/BNIP3-related mitophagy in hepatocytes DOI
Yifei Chen,

Fuji Yang,

Yujie Shi

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 219, P. 163 - 179

Published: April 13, 2024

Language: Английский

Citations

7