Hexokinase 1 cellular localization regulates the metabolic fate of glucose

Jesus, Adam De; Keyhani-Nejad, Farnaz; Pusec, Carolina M.; Goodman, Lauren; Geier, Justin; Stoolman, Joshua S.; Stanczyk, Paulina J.; Nguyen, Tivoli; Xu, Kai; Suresh, Krishna V.; Chen, Yihan; Rodriguez, Arianne E.; Shapiro, Jason S.; Chang, Hsiang-Chun; Chen, Chunlei; Shah, Kriti P.; Ben-Sahra, Issam; Layden, Brian T.; Chandel, Navdeep S.; Weinberg, Samuel E.; Ardehali, Hossein

doi:10.1016/j.molcel.2022.02.028

Cited by 52 publications

(44 citation statements)

References 75 publications

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“…HK is the ratelimiting enzyme for catalyzing glycolysis and interacts with the outer mitochondrial membrane protein VDAC 49 . HK mitochondrial binding protects mitochondrial function and neuron survival from ischemic injury and oxidative damage 19,50 , and further regulates in ammatory responses 51 . It was previously reported that PAR-dependent inhibition of HK-I leads to NAD + -independent glycolytic and bioenergetic failure in MNNG-induced parthanatos 21 .…”

Section: Discussionmentioning

confidence: 99%

Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I

Liu

Zhang

et al. 2022

Preprint

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Parthanatos is one of the major types of programmed cell death in ischemic stroke characterized by DNA damage, poly (ADP-ribose) polymerases (PARP) activation, and poly (ADP-ribose) (PAR) formation. Here we demonstrate that crocetin, a natural potent antioxidant compound from Crocus sativus, antagonizes parthanatos in ischemic stroke. We reveal that mechanistically, crocetin inhibits NADPH oxidase 2 (NOX2) activation to reduce reactive oxygen species (ROS) and PAR production at the early stage of parthanatos. Meanwhile we demonstrate that PARylated hexokinase-I (HK-I) is a novel substrate of E3 ligase RNF146 and that crocetin interact with HK-I to suppresses RNF146-mediated HK-I degradation at the late stage of parthanatos, preventing mitochondrial dysfunction and DNA damage that ultimately triggers the irreversible cell death. Our study supports further development of crocetin as a potential drug candidate for preventing and/or treating ischemic stroke.

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Section: Discussionmentioning

confidence: 99%

Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I

Liu

Zhang

et al. 2022

Preprint

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“…We discovered that when Hexokinase 1 (HK1) is dissociated from the mitochondria it results in a hyper-inflammatory response to LPS ( De Jesus et al., 2022 ). To determine the physiologic function of the HK1 mitochondrial binding domain (MBD), we generated a mouse model lacking the MBD of the endogenous HK1 protein, termed ΔE1HK1.…”

Section: Before You Beginmentioning

confidence: 99%

“…13 C-glucose labeling described ( De Jesus et al., 2022 ) show carbon enrichment in pathways of interest (specifically glycolysis and TCA cycle), but do not provide detailed information on in vivo metabolic flux since PMs are labeled outside of their endogenous niche. Although these cells represent a primary immune cell population, they are not reflective of in vivo metabolite flux since the isolation and plating process may causes changes in metabolite fluxes that deviate from endogenous levels.…”

Section: Limitationsmentioning

confidence: 99%

“…Our protocol can consistently extract metabolites from low cell number samples with fewer steps than methanol-based approaches. For complete details on the use and execution of this protocol, please refer to De Jesus et al., (2022 ).…”

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confidence: 99%

“…For complete details on the use and execution of this protocol, please refer to De Jesus et al., (2022 ).…”

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confidence: 99%

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Optimized protocol to isolate primary mouse peritoneal macrophage metabolites

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Nanozyme‐Based Regulation of Cellular Metabolism and Their Applications

Wang

Yin

et al. 2023

Advanced Materials

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Metabolism is the sum of the enzyme‐dependent chemical reactions, which produces energy in catabolic process and synthesizes biomass in anabolic process, exhibiting high similarity in mammalian cell, microbial cell, and plant cell. Consequently, the loss or gain of metabolic enzyme activity will greatly affect cellular metabolism. Nanozymes, as emerging enzyme mimics with diverse functions and adjustable catalytic activities, has shown attractive potential for metabolic regulation. Although the basic metabolic tasks are highly similar for the cells from different species, the concrete metabolic pathway varies with the intracellular structure of different species. In this review, we describe the basic metabolism in living organisms and discuss the similarities and differences in the metabolic pathways among mammalian, microbial and plant cells and the regulation mechanism. We then systematically review the recent progress on regulation of cellular metabolism mainly including nutrients uptake and utilization, energy production and the accompanied redox reactions by different kinds of oxidoreductases and their applications in the field of disease therapy, antimicrobial therapy, and sustainable agriculture. Furthermore, the prospects and challenges of nanozymes in regulating cell metabolism are also discussed, which will broaden their application scenarios.This article is protected by copyright. All rights reserved

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Hexokinase 1 cellular localization regulates the metabolic fate of glucose

Cited by 52 publications

References 75 publications

Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I

Crocetin antagonizes parthanatos in ischemic stroke via inhibiting NOX2 and preserving mitochondrial hexokinase-I

Optimized protocol to isolate primary mouse peritoneal macrophage metabolites

Nanozyme‐Based Regulation of Cellular Metabolism and Their Applications

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