Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Sita, Giulia; Hrelia, Patrizia; Graziosi, Agnese; Morroni, Fabiana

doi:10.3390/jcm9010126

Cited by 18 publications

(12 citation statements)

References 63 publications

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“…However, the balance can change to meet metabolic requirements, adapt to environmental stimuli or pathological conditions, or remove damaged organelles. Mitochondrial fusion is regulated by three GTPases, namely, Mfn1 and Mfn2 in the mitochondrial outer membrane and OPA1 in the intima (Sita et al, 2020 ). This process connects adjacent mitochondria together and merges their inner and outer membranes, ultimately forming a single mitochondrion.…”

Section: Discussionmentioning

confidence: 99%

Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease

Chen

Zhang

et al. 2021

Front. Aging Neurosci.

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Alzheimer’s disease (AD), the most common neurodegenerative disease in elderly humans, is pathologically characterized by amyloid plaques and neurofibrillary tangles. Mitochondrial dysfunction that occurs in the early stages of AD, which includes dysfunction in mitochondrial generation and energy metabolism, is considered to be closely associated with AD pathology. Selenomethionine (Se-Met) has been reported to improve cognitive impairment and reduce amyloid plaques and neurofibrillary tangles in 3xTg-AD mice. Whether Se-Met can regulate mitochondrial dysfunction in an AD model during this process remains unknown.In this study, the N2a-APP695-Swedish (N2aSW) cell and 8-month-old 3xTg-AD mice were treated with Se-Met in vitro and in vivo. Our study showed that the numbers of mitochondria were increased after treatment with Se-Met. Se-Met treatment also significantly increased the levels of NRF1 and Mfn2, and decreased those of OPA1 and Drp1. In addition, the mitochondrial membrane potential was significantly increased, while the ROS levels and apoptosis rate were significantly decreased, in cells after treatment with Se-Met. The levels of ATP, complex IV, and Cyt c and the activity of complex V were all significantly increased. Furthermore, the expression level of SELENO O was increased after Se-Met treatment. Thus, Se-Met can maintain mitochondrial dynamic balance, promote mitochondrial fusion or division, restore mitochondrial membrane potential, promote mitochondrial energy metabolism, inhibit intracellular ROS generation, and reduce apoptosis. These effects are most likely mediated via upregulation of SELENO O. In summary, Se-Met improves mitochondrial function by upregulating mitochondrial selenoprotein in these AD models.

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Section: Discussionmentioning

confidence: 99%

Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease

Chen

Zhang

et al. 2021

Front. Aging Neurosci.

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“…Here MFN2, an outer membrane mitochondria fusion protein, could maximize the oxidative capacity of the disease-free neurons, a potential response to a stressor associated with accumulation of pathologic Tau. MFN2 also inhibits mitochondrial fission, preventing autophagy, and thus helping to maintain mitochondria for the surviving neurons (Han et al, 2020; Sita et al, 2020; Wang et al, 2009). Given the role of neuron-mitochondrial dysfunction found in multiple models of AD, MFN2 may represent an important target for maintaining survival in proteopathy-susceptible neuron populations.…”

Section: Discussionmentioning

confidence: 99%

Single-cell Spatial Proteomic Imaging for Human Neuropathology

Vijayaragavan

Cannon

Tebaykin

et al. 2022

Preprint

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Neurodegenerative disorders are characterized by phenotypic changes and hallmark proteopathies. Quantifying these in archival human brain tissues remains indispensable for validating animal models and understanding disease mechanisms. We present a framework for nanometer-scale, spatial proteomics with multiplex ion beam imaging (MIBI) for capturing neuropathological features. MIBI facilitated simultaneous, quantitative imaging of 36 proteins on archival human hippocampus from individuals spanning cognitively normal to dementia. Customized analysis strategies identified cell types and proteopathies in the hippocampus across stages of Alzheimer’s disease (AD) neuropathologic change. We show microglia-pathologic tau interactions in hippocampal CA1 subfield, in AD dementia. Data driven, sample independent creation of spatial proteomic regions identified persistent neurons in pathologic tau neighborhoods expressing mitochondrial protein MFN2, regardless of cognitive status, suggesting a survival advantage. Our study revealed unique insights from multiplexed imaging and data-driven approaches for neuropathologic analysis and serves as a baseline for mechanistic and interventional understanding in human neurodegeneration.

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“…Besides, mitochondrial mobility and morphology dynamics are related to cytoskeleton proteins, 120 cellular energy metabolism, and Ca 2+ homeostasis. 121 And mitochondrial dynamics–related proteins are altered in many diseases, such as insulin resistanc, 122 type II diabetes, 123 neurodegenerative diseases, 124 Alzheimer’s disease, 125 cancer, 126 cardiovascular diseases, 127 and ischemic and dilated cardiomyopathy. 128,129 Dynamic changes in mitochondria are critical for mtDNA integrity, energy generation, and cellular processes such as calcium signaling and apoptosis regulation.…”

Section: Physiological Role Of Mitochondria In Chondrocytesmentioning

confidence: 99%

Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis

et al. 2021

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Purpose of Review Mitochondria are recognized to be one of the most important organelles in chondrocytes for their role in triphosphate (ATP) generation through aerobic phosphorylation. Mitochondria also participate in many intracellular processes involving modulating reactive oxygen species (ROS), responding to instantaneous hypoxia stress, regulating cytoplasmic transport of calcium ion, and directing mitophagy to maintain the homeostasis of individual chondrocytes. Designs To summarize the specific role of mitochondria in chondrocytes, we screened related papers in PubMed database and the search strategy is ((mitochondria) AND (chondrocyte)) AND (English [Language]). The articles published in the past 5 years were included and 130 papers were studied. Results In recent years, the integrity of mitochondrial structure has been regarded as a prerequisite for normal chondrocyte survival and defect in mitochondrial function has been found in cartilage-related diseases, such as osteoarthritis (OA) and rheumatoid arthritis (RA). However, the understanding of mitochondria in cartilage is still largely limited. The mechanism on how the changes in mitochondrial structure and function directly lead to the occurrence and development of cartilage-related diseases remains to be elusive. Conclusion This review aims to summarize the role of mitochondria in chondrocytes under the physiological and pathological changes from ATP generation, calcium homeostasis, redox regulation, mitophagy modulation, mitochondria biogenesis to immune response activation. The enhanced understanding of molecular mechanisms in mitochondria might offer some new cues for cartilage remodeling and pathological intervention.

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Back to The Fusion: Mitofusin-2 in Alzheimer’s Disease

Cited by 18 publications

References 63 publications

Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease

Selenomethionine Improves Mitochondrial Function by Upregulating Mitochondrial Selenoprotein in a Model of Alzheimer’s Disease

Single-cell Spatial Proteomic Imaging for Human Neuropathology

Role of Mitochondria in Physiology of Chondrocytes and Diseases of Osteoarthritis and Rheumatoid Arthritis

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