Mitochondrial fission

[This corrects the article DOI: 10.1016/j.apsb.2021.01.011.].

Mitochondria carry out essential functions in eukaryotic cells. The mitochondrial genome encodes factors critical to support oxidative phosphorylation and mitochondrial protein import necessary for these functions. However, organisms like budding yeast can readily lose their mitochondrial genome, yielding respiration-deficient petite mutants. The fission yeast Schizosaccharomyces pombe is petite-negative, but some nuclear mutations enable the loss of its mitochondrial genome. Here, we characterize the classical petite -positive mutation ptp1-1 as a loss of function allele of the proteasome 19S regulatory subunit component mts4/rpn1 , involved in the Ubiquitin-dependent degradation pathway...

Ultraviolet-B (UV-B) irradiation has been reported to cause oxidative stress and inflammation-mediated skin photo-damage. Furthermore, mitochondrial dynamics have been implicated to play a critical role in these processes. For the first time, we describe in this study how UVB-induced aberrant mitochondrial dynamics and inflammation interact in primary human dermal fibroblasts (HDFs). Our findings demonstrated that UV-B irradiation induced -impairment in mitochondrial dynamics by increasing mitochondrial fragmentation in HDFs...

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, can prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein...

Previous studies showed that NaIO3 can induce oxidative stress-mediated retinal pigment epithelium (RPE) damage to simulate age-related macular degeneration (AMD). Lemon peel is rich in antioxidants and components that can penetrate the blood-retinal barrier, but their role in retinal oxidative damage remains unexplored. Here, we explore the protection of lemon peel ultrasonic-assisted water extract (LUWE), containing large amounts of flavonoids and polyphenols, against NaIO3 -induced retinal degeneration. We initially demonstrated that LUWE, orally administered, prevented retinal distortion and thinning on the inner and outer nuclei layers, downregulating cleaved caspase-3 protein expression in RPE cells in NaIO3 -induced mice...

BACKGROUND: Cartilaginous endplate (CEP) degeneration, which is an important contributor to intervertebral disc degeneration (IVDD), is characterized by chondrocyte death. Accumulating evidence has revealed that dynamin-related protein 1 (Drp1)-mediated mitochondrial fission and dysfunction lead to apoptosis during CEP degeneration and IVDD. Exosomes are promising agents for the treatment of many diseases, including osteoporosis, osteosarcoma, osteoarthritis and IVDD. Despite their major success in drug delivery, the full potential of exosomes remains untapped...

Alzheimer's disease (AD) is a chronic neurodegenerative disease characterized by progressive memory loss and behavioral disorders. The excessive accumulation of amyloid β (Aβ) and the formation of neurofibrillary tangles (NFTs) damage synaptic connections and the death of neurons. However, the underlying mechanisms of pathogenesis of AD remain unclear. Growing evidence indicates that impaired mitochondrial function may play a crucial role in the development of AD. In the current study, we investigated whether nicotinic acid (NA) could protect against amyloid β1-42 -induced cytotoxicity in differentiated SH-SY5Y cells...

DEAD-box helicase 17 (DDX17) is a typical member of the DEAD-box family with transcriptional cofactor activity. Although DDX17 is abundantly expressed in the myocardium, its role in heart is not fully understood. We generated cardiomyocyte-specific Ddx17-knockout mice (Ddx17-cKO), cardiomyocyte-specific Ddx17 transgenic mice (Ddx17-Tg), and various models of cardiomyocyte injury and heart failure (HF). DDX17 is downregulated in the myocardium of mouse models of heart failure and cardiomyocyte injury. Cardiomyocyte-specific knockout of Ddx17 promotes autophagic flux blockage and cardiomyocyte apoptosis, leading to progressive cardiac dysfunction, maladaptive remodeling and progression to heart failure...

Ammonia-N poses a significant threat to aquatic animals. However, the mechanism of ROS production leading to DNA damage in hemocytes of crustaceans is still unclear. Additionally, the mechanism that cells respond to DNA damage by activating complex signaling networks has not been well studied. Therefore, we exposed shrimp to 0, 2, 10, and 20 mg/L NH4 Cl for 0, 3, 6, 12, 24, 48, and 72 h, and explored the alterations in endoplasmic reticulum stress and mitochondrial fission, DNA damage, repair, autophagy and apoptosis...

OBJECTIVE: The study aimed to investigate the effect of the SUMOylation status of Drp1 on mitochondrial fission in CDDP-treated HNSCC cells cultured under hypoxic conditions. MATERIALS AND METHODS: The effect of hypoxia on the chemosensitivity of HNCC cells was evaluated by flow cytometry and CCK-8 assays. The biological function of SUMO-specific peptidase 3 (SENP3) was evaluated by loss-of-function assays both in vitro and in vivo. SENP3-regulated deSUMOylation of Drp1 were performed with co-IP assays...

The peroxisomal disease adrenoleukodystrophy (X-ALD) is caused by loss of the transporter of very-long-chain fatty acids (VLCFAs), ABCD1. An excess of VLCFAs disrupts essential homeostatic functions crucial for axonal maintenance, including redox metabolism, glycolysis and mitochondrial respiration. As mitochondrial function and morphology are intertwined, we set out to investigate the role of mitochondrial dynamics in X-ALD models. Using quantitative 3D transmission electron microscopy, we revealed mitochondrial fragmentation in corticospinal axons in Abcd1- mice...

Intestinal ischemia‒reperfusion (IIR) injury is a common complication of surgery, but clear molecular insights and valuable therapeutic targets are lacking. Mitochondrial calcium overload is an early sign of various diseases and is considered a vital factor in ischemia‒reperfusion injury. The mitochondrial calcium uniporter (MCU), which is located on the inner mitochondrial membrane, is the primary mediator of calcium ion entry into the mitochondria. However, the specific mechanism of MCU in IIR injury remains to be clarified...

Mitochondria are central to cellular energy production and metabolic regulation, particularly in cardiomyocytes. These organelles constantly undergo cycles of fusion and fission, orchestrated by key proteins like Dynamin-related Protein 1 (Drp-1). This review focuses on the intricate roles of Drp-1 in regulating mitochondrial dynamics, its implications in cardiovascular health, and particularly in myocardial infarction. Drp-1 is not merely a mediator of mitochondrial fission; it also plays pivotal roles in autophagy, mitophagy, apoptosis, and necrosis in cardiac cells...

Early handling (EH), the brief separation of pups from their mother during early life, has been shown to exert beneficial effects. However, the impact of EH in a high anxiety background as well as the role of brain mitochondria in shaping EH-driven responses remain elusive.Here, we used a high (HAB) vs. normal (NAB) anxiety-related behavior mouse model to study how EH affects pup and dam behavior in divergent anxiety backgrounds. We also investigated EH-induced effects at the protein and mRNA levels in adult male HAB mice in the hypothalamus, the prefrontal cortex, and the hippocampus by examining the same mitochondrial/energy pathways and mitochondrial dynamics mechanisms (fission, fusion, biogenesis, and mitophagy) in all three brain regions...

Continuous fusion and fission are critical for mitochondrial health. In this study, we further characterize the role played by dynamin-related protein 1 (Drp1) in mitochondrial fission. We show that a single amino acid change in Drp1 at position 39 from serine to alanine (S39A) within the GTP-binding (GTPase) domain results in a fused mitochondrial network in human SH-SY5Y neuroblastoma cells. Interestingly, the phosphorylation of Ser-616 and Ser-637 of Drp1 remains unaffected by the S39A mutation, and mitochondrial bioenergetic profile and cell viability in the S39A mutant were comparable to those observed in the control...

Disturbance in mitochondrial homeostasis within proximal tubules is a critical characteristic associated with diabetic kidney disease (DKD). CaMKKβ/AMPK signaling plays an important role in regulating mitochondrial homeostasis. Despite the downregulation of CaMKKβ in DKD pathology, the underlying mechanism remains elusive. The expression of NEDD4L, which is primarily localized to renal proximal tubules, is significantly upregulated in the renal tubules of mice with DKD. Coimmunoprecipitation (Co-IP) assays revealed a physical interaction between NEDD4L and CaMKKβ...

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Sepsis-induced acute kidney injury (SAKI) poses a significant clinical challenge with high morbidity and mortality. Excessive mitochondrial fission has been identified as the central pathogenesis of sepsis-associated organ damage, which is also implicated in the early stages of SAKI. Sirtuin 5 (SIRT5) has emerged as a central regulator of cellular mitochondrial function; however, its role in the regulation of sepsis-induced excessive mitochondrial fission in kidney and the underlying mechanism remains unclear...

Phenotypic shift of vascular smooth muscle cells (VSMCs) plays a key role in intimal hyperplasia, especially in patients with diabetes mellitus (DM). This study aimed to investigate the role of dynamin-related protein 1 (DRP1) in mitochondrial fission-mediated VSMC phenotypic shift and to clarify whether DRP1 is the therapeutic target of isoliquiritigenin (ISL). Wire injury of carotid artery or platelet-derived growth factor treatment was performed in DM mice or high-glucose cultured human aortic smooth muscle cells (HASMCs), respectively...

AIMS: With a focus on the discrepancy between preclinical and clinical findings, this review will gather comprehensive information about the effects of calcineurin inhibitors (CNI) on cognitive function and related brain pathology from in vitro, in vivo, and clinical studies. We also summarize the potential mechanisms that underlie the pathways related to CNI-induced cognitive impairment. METHODS: We systematically searched articles in PubMed using keywords 'calcineurin inhibitor*' and 'cognition' to identify related articles, which the final list pertaining to underlying mechanisms of CNI on cognition...