Sleep/wake calcium dynamics, respiratory function, and ROS production in cardiac mitochondria

Abdel‐Rahman, Engy A.; Hosseiny, Salma; Aaliya, Abdullah; Adel, Mohamed; Yasseen, Basma A; AlOkda, Abdelrahman; Radwan, Yasmine; Saber, Saber H.; Elkholy, Nada; Elhanafy, Eslam; Walker, Emily E.; Zuniga-Hertz, Juan Pablo; Patel, Hemal H.; Griffiths, Helen R.; Ali, Sameh S.

doi:10.1016/j.jare.2021.01.006

Cited by 24 publications

(15 citation statements)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria serve as the primary organelles for reactive oxygen species (ROS) production in cardiomyocytes [ 7 ]. Cardiac aging is accompanied by a decline in mitochondrial function, accumulation of dysfunctional mitochondria, increased ROS production, and dysregulated mitochondrial quality control [ 8 , 9 ]. Damaged mitochondria cannot be easily cleared away via cell division, given their insufficient ability to proliferate and dilute damaged mitochondria through cell division.…”

Section: Introductionmentioning

confidence: 99%

Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy

Wang¹,

Xu²,

W³

et al. 2022

Redox Biology

View full text Add to dashboard Cite

Section: Introductionmentioning

confidence: 99%

Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy

Wang¹,

Xu²,

W³

et al. 2022

Redox Biology

View full text Add to dashboard Cite

“…For example, nuclear factor-erythroid 2-related factor 2 (NRF2) serves as a redox-responsive factor and mediates ROS elimination, 256 while downregulation of NRF2 is observed in elderly individuals. As expected, reduced ROS production or the oxidized form of glutathione (GSSG) disposition ameliorates cardiac aging, 257,258 supporting the concept that ROS derived by mitochondria are harmful to aging hearts. Recently, the correlation between ROS with cardiac aging is reported in some preclinical studies.…”

Section: Mitochondrial Ros and Mtdnamentioning

confidence: 54%

Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications

Xie

Deng

et al. 2023

Sig Transduct Target Ther

View full text Add to dashboard Cite

Cardiac aging is evident by a reduction in function which subsequently contributes to heart failure. The metabolic microenvironment has been identified as a hallmark of malignancy, but recent studies have shed light on its role in cardiovascular diseases (CVDs). Various metabolic pathways in cardiomyocytes and noncardiomyocytes determine cellular senescence in the aging heart. Metabolic alteration is a common process throughout cardiac degeneration. Importantly, the involvement of cellular senescence in cardiac injuries, including heart failure and myocardial ischemia and infarction, has been reported. However, metabolic complexity among human aging hearts hinders the development of strategies that targets metabolic susceptibility. Advances over the past decade have linked cellular senescence and function with their metabolic reprogramming pathway in cardiac aging, including autophagy, oxidative stress, epigenetic modifications, chronic inflammation, and myocyte systolic phenotype regulation. In addition, metabolic status is involved in crucial aspects of myocardial biology, from fibrosis to hypertrophy and chronic inflammation. However, further elucidation of the metabolism involvement in cardiac degeneration is still needed. Thus, deciphering the mechanisms underlying how metabolic reprogramming impacts cardiac aging is thought to contribute to the novel interventions to protect or even restore cardiac function in aging hearts. Here, we summarize emerging concepts about metabolic landscapes of cardiac aging, with specific focuses on why metabolic profile alters during cardiac degeneration and how we could utilize the current knowledge to improve the management of cardiac aging.

show abstract

“…More recent evidence indicates that many cation channels can be regulated over daily time ( Abdel-Rahman et al, 2021 ). We thus wondered whether the protein levels of Letm1 might change across the day.…”

Section: Resultsmentioning

confidence: 99%

“…This observation raises the question of whether internal clocks also set the pace of mitochondrial solute carriers and H + -cation exchangers, as these are critical for chemiosmotic processes. In this context, a correlative study between diurnal fluctuation of cardiac OXPHOS and Ca 2+ dynamics has shown increased activity of the mitochondrial Na + /Ca 2+ exchanger and Ca 2+ transporters, as well as a higher mitochondrial Ca 2+ retention capacity at night than in the day, and attributed the increased cardiac daytime vulnerability to reduced daytime mitochondrial Ca 2+ dynamics ( Abdel-Rahman et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

The cation exchanger Letm1, circadian rhythms, and NAD(H) levels interconnect in diurnal zebrafish

et al. 2022

View full text Add to dashboard Cite

Mitochondria are fundamental for life and require balanced ion exchange to maintain proper functioning. The mitochondrial cation exchanger LETM1 sparks interest because of its pathophysiological role in seizures in the Wolf Hirschhorn Syndrome (WHS). Despite observation of sleep disorganization in epileptic WHS patients, and growing studies linking mitochondria and epilepsy to circadian rhythms, LETM1 has not been studied from the chronobiological perspective. Here we established a viable letm1 knock-out, using the diurnal vertebrate Danio rerio to study the metabolic and chronobiological consequences of letm1 deficiency. We report diurnal rhythms of Letm1 protein levels in wild-type fish. We show that mitochondrial nucleotide metabolism is deregulated in letm1−/− mutant fish, the rate-limiting enzyme of NAD+ production is up-regulated, while NAD+ and NADH pools are reduced. These changes were associated with increased expression amplitude of circadian core clock genes in letm1−/− compared with wild-type under light/dark conditions, suggesting decreased NAD(H) levels as a possible mechanism for circadian system perturbation in Letm1 deficiency. Replenishing NAD pool may ameliorate WHS-associated sleep and neurological disorders.

show abstract

Sleep/wake calcium dynamics, respiratory function, and ROS production in cardiac mitochondria

Abstract: Graphical abstract Sleep/wake cycle-dependent differences in molecular parameters controlling mitochondrial ability to regulate cellular levels of calcium and associated ROS production.

Cited by 24 publications

References 72 publications

Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy

Ablation of Shank3 alleviates cardiac dysfunction in aging mice by promoting CaMKII activation and Parkin-mediated mitophagy

Metabolic landscape in cardiac aging: insights into molecular biology and therapeutic implications

The cation exchanger Letm1, circadian rhythms, and NAD(H) levels interconnect in diurnal zebrafish

Contact Info

Product

Resources

About