Mitochondrial and Metabolic Adaptations to Exercise-Induced Fluid Shear Stress in Endothelial Cells

Hong, Soon‐Gook; Shin, Junchul; Aldokhayyil, Maitha; Brown, Michael D.; Park, Joon‐Young

doi:10.1249/jes.0000000000000289

Cited by 8 publications

(5 citation statements)

References 51 publications

(75 reference statements)

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“…Changes in the magnitude and the pattern of hemodynamic flow induce mitochondrial remodeling and metabolic reprogramming. As reviewed in (Hong et al., 2022), several studies have focused on metabolic reprogramming within endothelial cells subjected to laminar shear stress or oscillatory shear stress. Laminar shear stress is associated with an increase in mitochondrial respiration, a decrease in glycolysis and an upregulation of lipid metabolism (Kim et al., 2014; Doddaballapur et al., 2015; Feng et al., 2017; Wu et al., 2017; Venturini et al., 2019).…”

Section: Mitochondrial Mechanics and Metabolism Are Reciprocally Regu...mentioning

confidence: 99%

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Villard

Manneville

2023

Biology of the Cell

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Metabolism and mechanics are two key facets of structural and functional processes in cells, such as growth, proliferation, homeostasis and regeneration. Their reciprocal regulation has been increasingly acknowledged in recent years: external physical and mechanical cues entail metabolic changes, which in return regulate cell mechanosensing and mechanotransduction. Since mitochondria are pivotal regulators of metabolism, we review here the reciprocal links between mitochondrial morphodynamics, mechanics and metabolism. Mitochondria are highly dynamic organelles which sense and integrate mechanical, physical and metabolic cues to adapt their morphology, the organization of their network and their metabolic functions. While some of the links between mitochondrial morphodynamics, mechanics and metabolism are already well established, others are still poorly documented and open new fields of research. First, cell metabolism is known to correlate with mitochondrial morphodynamics. For instance, mitochondrial fission, fusion and cristae remodeling allow the cell to fine‐tune its energy production through the contribution of mitochondrial oxidative phosphorylation and cytosolic glycolysis. Second, mechanical cues and alterations in mitochondrial mechanical properties reshape and reorganize the mitochondrial network. Mitochondrial membrane tension emerges as a decisive physical property which regulates mitochondrial morphodynamics. However, the converse link hypothesizing a contribution of morphodynamics to mitochondria mechanics and/or mechanosensitivity has not yet been demonstrated. Third, we highlight that mitochondrial mechanics and metabolism are reciprocally regulated, although little is known about the mechanical adaptation of mitochondria in response to metabolic cues. Deciphering the links between mitochondrial morphodynamics, mechanics and metabolism still presents significant technical and conceptual challenges but is crucial both for a better understanding of mechanobiology and for potential novel therapeutic approaches in diseases such as cancer.

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Section: Mitochondrial Mechanics and Metabolism Are Reciprocally Regu...mentioning

confidence: 99%

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Villard

Manneville

2023

Biology of the Cell

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“…Figure 5b summarizes what is currently known regarding the effects of SS and OS on mitochondrial and EC function: Prolonged SS is thought to maintain ΔΨ m and the mitochondrial network morphology, and, via mitochondrial biogenesis (≥72 h), improve ATP production (Hong, Shin, Aldokhayyil, et al, 2022 ). OS in vitro and d‐flow in vivo resulted in increased mitochondrial fission compared to SS in vitro and s‐flow in vivo, respectively (Hong, Shin, Choi, et al, 2022 ), although not every report was in agreement (Coon et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

“…OS in vitro and d‐flow in vivo resulted in increased mitochondrial fission compared to SS in vitro and s‐flow in vivo, respectively (Hong, Shin, Choi, et al, 2022 ), although not every report was in agreement (Coon et al, 2022 ). It is well accepted that SS results in active mitophagy, increases Klf2/eNOS, decreases mROS and ROS, suppresses inflammation and protects ECs from apoptosis in response to an additional stimulus, whereas OS causes the opposite trends (Coon et al, 2022 ; Dai et al, 2007 ; Hong, Shin, Aldokhayyil, et al, 2022 ; Scheitlin et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Modulation of the mitochondrial Ca²⁺ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells

Patel

Pietromicca

Venkatesan

et al. 2023

Physiological Reports

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Mitochondrial calcium ( m Ca 2+ ) uptake occurs via the Mitochondrial Ca 2+ Uniporter (MCU) complex and plays a critical role in mitochondrial dynamics, mitophagy, and apoptosis. MCU complex activity is in part modulated by the expression of its regulatory subunits. Cardiovascular disease models demonstrated altered gene/protein expression of one or multiple subunits in different cells, including vascular endothelial cells (ECs). MCU complex activity was found necessary for stable flow (s‐flow)‐induced mitophagy and promotion of an atheroprotective EC phenotype. Disturbed flow (d‐flow) is known to lead to an atheroprone phenotype. Despite the role of MCU in flow‐regulated EC function, flow‐induced alterations in MCU complex subunit expression are currently unknown. We exposed cultured human ECs to atheroprotective (steady shear stress, SS) or atheroprone flow (oscillatory shear stress, OS) and measured mRNA and protein levels of the MCU complex members. SS and OS differentially modulated subunit expression at gene/protein levels. Protein expression changes of the core MCU, m Ca 2+ uptake 1 (MICU1) and MCU regulator 1 (MCUR1) subunits in SS‐ and OS‐exposed, compared to static, ECs suggested an enhanced m Ca 2+ influx under each flow and a potential contribution to EC dysfunction under OS. In silico analysis of a single‐cell RNA‐sequencing dataset was employed to extract transcript values of MCU subunits in mouse carotid ECs from regions exposed to s‐flow or d‐flow. Mcu and Mcur1 genes showed significant differences in expression after prolonged exposure to each flow. The differential expression of MCU complex subunits indicated a tight regulation of the complex activity under physiological and pathological hemodynamic conditions.

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“…Thus, in the present study, NRs were considered for those participants who decreased a –1 mmHg in blood pressure. The mechanisms of how exercise decreases blood pressure could be potentially explained by 1) angiogenesis in the skeletal muscle ( Fernandes et al, 2012 ), 2) a reduction of the peripheral vascular resistance ( Correia et al, 2015 ), 3) a reduction of the arterial stiffness ( Guimaraes et al, 2010 ), 4) improvements in the endothelial function ( Ramirez-Jimenez et al, 2017 ), 5) an increase in production and action of nitric oxide levels ( Izadi et al, 2018 ), 6) an increase in the major baroreflex control ( Somers et al, 1991 ), and also by the 6) increased shear stress produced by exercise in the arterial wall ( Hong et al, 2022 ), and, thus, a major arterial distensibility ( Kobayashi et al, 2022 ).…”

Section: Discussionmentioning

confidence: 99%

Characterizing the interindividual postexercise hypotension response for two order groups of concurrent training in patients with morbid obesity

et al. 2022

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Background: Postexercise hypotension (PEH) is a common physiological phenomenon occurring immediately after endurance training (ET), resistance training (RT), and ET plus RT, also termed concurrent training (CT); however, there is little knowledge about the interindividual and magnitude response of PEH in morbidly obese patients.Aim: The aims of this study were (1) to investigate the effect of CT order (ET + RT vs. RT + ET) on the blood pressure responses; 2) characterize these responses in responders and nonresponders, and 3) identify potential baseline outcomes for predicting blood pressure decreases as responders.Methods: A quasi-experimental study developed in sedentary morbidly obese men and women (age 43.6 ± 11.3 years; body mass index [BMI] ≥40 kg/m2) was assigned to a CT group of ET plus RT (ET + RT; n = 19; BMI 47.8 ± 16.7) or RT plus ET order group (RT + ET; n = 17; BMI 43.0 ± 8.0). Subjects of both groups received eight exercise sessions over four weeks. Primary outcomes include systolic (SBP), diastolic (DBP), mean arterial pressure [MAP], heart rate at rest [HR], and pulse pressure [PP] measurements before and after 10 min post-exercise. Secondary outcomes were other anthropometric, body composition, metabolic, and physical fitness parameters. Using the delta ∆SBP reduction, quartile categorization (Q) in “high” (Rs: quartile 4), “moderate” (MRs: quartile 3), “low” (LRs: quartile 2), and “nonresponders” (NRs: quartile 1) was reported.Results: Significant pre–post changes were observed in ET + RT in session 2 for SBP (131.6 vs. 123.4 mmHg, p = 0.050) and session 4 (131.1 vs. 125.2 mmHg, p = 0.0002), while the RT + ET group showed significant reductions in session 4 (134.2 vs. 125.3 mmHg, p < 0.001). No significant differences were detected in the sum of the eight sessions for SBP (∑∆SBP) between ET + RT vs. RT + ET (−5.7 vs. −4.3 mmHg, p = 0.552). Interindividual analyses revealed significant differences among frequencies comparing Q1 “NRs” (n = 8; 22.2%), Q2 “LRs” (n = 8; 22.2%), Q3 “MRs” (n = 9; 25.0%), and Q4 “HRs” (n = 11; 30.5%), p < 0.0001. Quartile comparisons showed significant differences in SBP changes (p = 0.035). Linear regression analyses revealed significant association between ∑∆SBP with body fat % (β –3.826, R2 0.211 [21.1%], p = 0.031), skeletal muscle mass [β –2.150, R2 0.125 (12.5%), p = 0.023], fasting glucose [β 1.273, R2 0.078 (7.8%), p = 0.003], triglycerides [β 0.210, R2 0.014 (1.4%), p = 0.008], and the 6-min walking test [β 0.183, R2 0.038 (3.8%), p = 0.044].Conclusion: The CT order of ET + RT and RT + ET promote a similar ‘magnitude’ in the postexercise hypotensive effects during the eight sessions of both CT orders in 4 weeks of training duration, revealing “nonresponders” and ‘high’ responders that can be predicted from body composition, metabolic, and physical fitness outcomes.

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Mitochondrial and Metabolic Adaptations to Exercise-Induced Fluid Shear Stress in Endothelial Cells

Abstract: Exercise-mediated hemodynamic flow confers mitochondrial remodeling and metabolic reprogramming in the vascular endothelial cell.

Cited by 8 publications

References 51 publications

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Modulation of the mitochondrial Ca²⁺ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells

Characterizing the interindividual postexercise hypotension response for two order groups of concurrent training in patients with morbid obesity

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Mitochondrial and Metabolic Adaptations to Exercise-Induced Fluid Shear Stress in Endothelial Cells

Abstract: Exercise-mediated hemodynamic flow confers mitochondrial remodeling and metabolic reprogramming in the vascular endothelial cell.

Cited by 8 publications

References 51 publications

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Mitochondria: At the crossroads between mechanobiology and cell metabolism

Modulation of the mitochondrial Ca2+ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells

Characterizing the interindividual postexercise hypotension response for two order groups of concurrent training in patients with morbid obesity

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Modulation of the mitochondrial Ca²⁺ uniporter complex subunit expression by different shear stress patterns in vascular endothelial cells