Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: Novel therapeutic targets for neurodegenerative diseases

He, Qiong; Qu, Meiyu; Shen, Tingyu; Su, Jiakun; Xu, Yuhao; Xu, Chengyun; Barkat, Muhammad Qasim; Cai, Jing; Zhu, Hai‐Bin; Zeng, Ling‐Hui; Wu, Ximei

doi:10.1016/j.arr.2023.101920

Cited by 14 publications

(6 citation statements)

References 208 publications

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“…Vance, scholars defined ERMCSs as dynamic lipid rafts spanning 10−30 nm between the mitochondrial membrane and the ER membrane and studied the function of proteins in ERMCSs, such as Mfn1, Mfn2, VDAC1, Grp75, IP3R, VAPB, PTPTIP51, and PACS2. 15,43 However, the effect of hesperidin on the formation and function of ERMCSs in piglets is rarely reported. Therefore, we employed a wide-used oxidative stress model in piglets to investigate the effects of hesperidin on the formation of ERMCSs in jejunum.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, as a physical contact composed with a series of proteins on the outer mitochondrial membrane and the ER membrane, the ERMCSs have garnered growing attention from researchers in life sciences and have been demonstrated as a signaling hub controlling cell physiology. ,, Since the discovery of ERMCSs by J.E. Vance, scholars defined ERMCSs as dynamic lipid rafts spanning 10–30 nm between the mitochondrial membrane and the ER membrane and studied the function of proteins in ERMCSs, such as Mfn1, Mfn2, VDAC1, Grp75, IP3R, VAPB, PTPTIP51, and PACS2. , However, the effect of hesperidin on the formation and function of ERMCSs in piglets is rarely reported. Therefore, we employed a wide-used oxidative stress model in piglets to investigate the effects of hesperidin on the formation of ERMCSs in jejunum.…”

Section: Discussionmentioning

confidence: 99%

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Hesperidin Alleviated Intestinal Barrier Injury, Mitochondrial Dysfunction, and Disorder of Endoplasmic Reticulum Mitochondria Contact Sites under Oxidative Stress

Gou,

Lin,

et al. 2024

J. Agric. Food Chem.

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As primary flavonoids extracted from citrus fruits, hesperidin has been attracting attention widely for its capacity to act as antioxidants that are able to scavenge free radicals and reactive oxygen species (ROS). Many factors have made oxidative stress a risk factor for the occurrence of intestinal barrier injury, which is a serious health threat to human beings. However, little data are available regarding the underlying mechanism of hesperidin alleviating intestinal injury under oxidative stress. Recently, endoplasmic reticulum (ER) mitochondria contact sites (ERMCSs) have aroused increasing concerns among scholars, which participate in mitochondrial dynamics and Ca 2+ transport. In our experiment, 24 piglets were randomly divided into 4 groups. Piglets in the diquat group and hesperidin + diquat group received an intraperitoneal injection of diquat (10 mg/kg), while piglets in the hesperidin group and hesperidin + diquat group received hesperidin (300 mg/kg) with feed. The results indicated that hesperidin alleviated growth restriction and intestinal barrier injury in piglets compared with the diquat group. Hesperidin ameliorated oxidative stress and restored antioxidant capacity under diquat exposure. The mitochondrial dysfunction was markedly alleviated via hesperidin versus diquat group. Meanwhile, hesperidin alleviated ER stress and downregulated the PERK pathway. Furthermore, hesperidin prevented the disorder of ERMCSs by downregulating the level of ERMCS proteins, decreasing the percentage of mitochondria with ERMCSs/total mitochondria and the ratio of ERMCSs length/mitochondrial perimeter. These results suggested hesperidin could alleviate ERMCS disorder and prevent mitochondrial dysfunction, which subsequently decreased ROS production and alleviated intestinal barrier injury of piglets under oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Hesperidin Alleviated Intestinal Barrier Injury, Mitochondrial Dysfunction, and Disorder of Endoplasmic Reticulum Mitochondria Contact Sites under Oxidative Stress

Gou,

Lin,

et al. 2024

J. Agric. Food Chem.

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“… 80 In some spatially constrained domains, such as the proximal ER-mitochondria contact sites (also termed ‘mitochondria-associated membranes, MAMs’), calcium release is concentrated, and regulated by PTMs. 81 , 82 The structural basis of the calcium release-associated MAMs is a series of tethering complexes that contain both subdomains from ER and mitochondria, such as vesicle-associated membrane protein-associated protein B (VAPB) on the ER and protein tyrosine phosphatase interacting protein 51 (PTPIP51) on the mitochondria (i.e., VAPB-PTPIP51); the inositol triphosphate receptor (IP3R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion (VDAC1) and sporadic PD-related protein DJ1 complex; mitofusin-2 (Mfn2) on the ER with Mfn1/Mfn2 on the OMM; Rho GTPases Miro1 and Miro2; and others. 83 – 87 In aged endothelial cells, the enhancement of MAMs is associated with increased mitochondrial Ca 2+ uptake but also cell death.…”

Section: Mitochondrial As Signaling Hubs In Defining Cell Fatementioning

confidence: 99%

Mitochondrial dysfunction: mechanisms and advances in therapy

Zong,

Li,

Liao

et al. 2024

Sig Transduct Target Ther

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Mitochondria, with their intricate networks of functions and information processing, are pivotal in both health regulation and disease progression. Particularly, mitochondrial dysfunctions are identified in many common pathologies, including cardiovascular diseases, neurodegeneration, metabolic syndrome, and cancer. However, the multifaceted nature and elusive phenotypic threshold of mitochondrial dysfunction complicate our understanding of their contributions to diseases. Nonetheless, these complexities do not prevent mitochondria from being among the most important therapeutic targets. In recent years, strategies targeting mitochondrial dysfunction have continuously emerged and transitioned to clinical trials. Advanced intervention such as using healthy mitochondria to replenish or replace damaged mitochondria, has shown promise in preclinical trials of various diseases. Mitochondrial components, including mtDNA, mitochondria-located microRNA, and associated proteins can be potential therapeutic agents to augment mitochondrial function in immunometabolic diseases and tissue injuries. Here, we review current knowledge of mitochondrial pathophysiology in concrete examples of common diseases. We also summarize current strategies to treat mitochondrial dysfunction from the perspective of dietary supplements and targeted therapies, as well as the clinical translational situation of related pharmacology agents. Finally, this review discusses the innovations and potential applications of mitochondrial transplantation as an advanced and promising treatment.

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“…There are also proteins in the ER that can be dynamically regulated by palmitoylation ( Harada et al, 2020 ). Dynamic coupling between mitochondria and the ER forms a new subcellular structure, the MAM (mitochondria-associated endoplasmic reticulum membrane), which is strongly implicated in NDs (neurodegenerative disorders) ( He et al, 2023 ). The ER can be coupled to mitochondria in addition to being tethered to the PM via junctophilins (JPH1-JPH4).…”

Section: Role Of Zdhhcs In Neurobiologymentioning

confidence: 99%

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

Liao,

Huang,

Liu

et al. 2024

Front. Pharmacol.

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S-palmitoylation is a reversible posttranslational modification, and the palmitoylation reaction in human-derived cells is mediated by the zDHHC family, which is composed of S-acyltransferase enzymes that possess the DHHC (Asp-His-His-Cys) structural domain. zDHHC proteins form an autoacylation intermediate, which then attaches the fatty acid to cysteine a residue in the target protein. zDHHC proteins sublocalize in different neuronal structures and exert dif-ferential effects on neurons. In humans, many zDHHC proteins are closely related to human neu-rological disor-ders. This review focuses on a variety of neurological disorders, such as AD (Alz-heimer’s disease), HD (Huntington’s disease), SCZ (schizophrenia), XLID (X-linked intellectual disability), attention deficit hyperactivity disorder and glioma. In this paper, we will discuss and summarize the research progress regarding the role of zDHHC proteins in these neu-rological disorders.

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Control of mitochondria-associated endoplasmic reticulum membranes by protein S-palmitoylation: Novel therapeutic targets for neurodegenerative diseases

Cited by 14 publications

References 208 publications

Hesperidin Alleviated Intestinal Barrier Injury, Mitochondrial Dysfunction, and Disorder of Endoplasmic Reticulum Mitochondria Contact Sites under Oxidative Stress

Hesperidin Alleviated Intestinal Barrier Injury, Mitochondrial Dysfunction, and Disorder of Endoplasmic Reticulum Mitochondria Contact Sites under Oxidative Stress

Mitochondrial dysfunction: mechanisms and advances in therapy

The role of s-palmitoylation in neurological diseases: implication for zDHHC family

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