The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain DOI Creative Commons

Jule Gerlach,

Paola Pireddu,

Xiaoqun Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

Abstract The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations genes have been linked to severe disorders, including Parkinson’s disease amyotrophic lateral sclerosis. In cultured cells, a fraction of oligomerize form high molecular weight complex unknown function. Here, we generated whole-body Chchd2 knockout mouse investigate vivo role its protein complex. We show that is crucial for sustaining full motor capacity, normal striatal dopamine levels, lipid homeostasis brain adult male mice. also demonstrate tissues, exist exclusively as complex, whose levels finely tuned under physiological conditions. response dysfunction, abundance size CHCHD2-CHCHD10 increases, mechanism across different tissues. Although loss does not abolish oligomerization, it enhances cell vulnerability stress, suggesting protective against damage. Our findings uncover preserving tissue provide important insights into involvement human diseases.

Language: Английский

Mitochondrial oxygen metabolism as a potential predictor of weight loss after laparoscopic sleeve gastrectomy for class III obesity DOI Creative Commons

Markus Engelmann,

Juliane Götze, Philipp Baumbach

et al.

Frontiers in Endocrinology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 7, 2025

The prevalence of obesity is increasing at an alarming rate in industrialized countries. Obesity a systemic disease that causes not only macroscopic alterations, but also mitochondrial dysfunction. Laparoscopic sleeve gastrectomy (LSG) poses potential therapeutic option for patients with severe obesity. In order to ascertain the efficacy bariatric interventions, it important assess weight loss, changes body composition. Additionally, aim this study was investigate association between loss and cellular oxygen metabolism, surrogate function. We used bioimpedance analysis (BIA) composition up one year after LSG. To evaluate we Cellular Oxygen Metabolism Monitor (COMET) non-invasively measure tension (mitoPO2), consumption (mitoVO2) delivery (mitoDO2). compared values obtained those age- sex-matched healthy controls investigated 48 (46.5 years [35.5-55.3]; 38/48 female (79.2%); BMI 46.7 [42.5-51.0]) completed study. They showed significant decrease relative fat mass six months. found no differences metabolism obese controls. MitoPO2, mitoVO2 mitoDO2 did change surgery. It noteworthy who exhibited higher mitoPO2, mitoVO2, prior surgery demonstrated superior outcomes This first measured long-term course Further studies larger cohorts are needed confirm these findings. https://www.bfarm.de/DE/Das-BfArM/Aufgaben/Deutsches-Register-Klinischer-Studien/_node.html, identifier DRKS00015891.

Language: Английский

Citations

1
Bridging lipid metabolism and mitochondrial genome maintenance DOI Creative Commons

C W Boone,

Samantha C. Lewis

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107498 - 107498

Published: June 27, 2024

Language: Английский

Citations

6
Mitofusin 2 displays fusion-independent roles in proteostasis surveillance DOI Creative Commons
Mariana Joaquim,

Selver Altin,

Maria-Bianca Bulimaga

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 10, 2025

Abstract Mitochondria are essential organelles and their functional state dictates cellular proteostasis. However, little is known about the molecular gatekeepers involved, especially in absence of external stress. Here we identify a role MFN2 quality control independent its function organellar shape remodeling. ablation alters proteome, marked for example by decreased levels import machinery accumulation kinase PINK1. Moreover, interacts with proteasome cytosolic chaperones, thereby preventing aggregation newly translated proteins. Similarly to MFN2-KO cells, patient fibroblasts MFN2-disease variants recapitulate excessive protein defects. Restoring re-establishes proteostasis cells rescues fusion defects MFN1-KO cells. In contrast, MFN1 loss or mitochondrial alterations do not alter aggregation, consistent fusion-independent homeostasis. sum, our findings open new possibilities therapeutic strategies modulation levels.

Language: Английский

Citations

0
Mitochondrial mt12361A>G increased risk of metabolic dysfunction-associated steatotic liver disease among non-diabetes DOI
Ming‐Ying Lu, Yu‐Ju Wei, Chih‐Wen Wang

et al.

World Journal of Gastroenterology, Journal Year: 2025, Volume and Issue: 31(10)

Published: Feb. 26, 2025

BACKGROUND Insulin resistance, lipotoxicity, and mitochondrial dysfunction contribute to the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). Mitochondrial impairs oxidative phosphorylation increases reactive oxygen species production, leading steatohepatitis hepatic fibrosis. Artificial intelligence (AI) is a potent tool for diagnosis risk stratification. AIM To investigate DNA polymorphisms in susceptibility MASLD establish an AI model screening. METHODS Multiplex polymerase chain reaction was performed comprehensively genotype 82 variants screening dataset (n = 264). The significant single nucleotide polymorphism validated independent cohort 1046) using Taqman® allelic discrimination assay. Random forest, eXtreme gradient boosting, Naive Bayes, logistic regression algorithms were employed construct MASLD. RESULTS In dataset, only mt12361A>G significantly associated with showed borderline significance patients 2-3 cardiometabolic traits compared controls validation (P 0.055). Multivariate analysis confirmed that factor [odds ratio (OR) 2.54, 95% confidence interval (CI): 1.19-5.43, P 0.016]. genetic effect non-diabetic group but not diabetic group. mt12361G carriers had 2.8-fold higher than A (OR 2.80, 95%CI: 1.22-6.41, 0.015). By integrating clinical features mt12361A>G, random forest outperformed other detecting [training area under receiver operating characteristic curve (AUROC) 1.000, AUROC 0.876]. CONCLUSION variant increased severity patients. supports management primary care settings.

Language: Английский

Citations

0
Mitochondrial genetics, signalling and stress responses DOI
Yasmine J. Liu, Jonathan Sulc, Johan Auwerx

et al.

Nature Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Language: Английский

Citations

0
The fate of mitochondrial respiratory complexes in aging DOI Creative Commons
Hanna Salmonowicz, Karolina Szczepanowska

Trends in Cell Biology, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

While mitochondrial dysfunction is one of the canonical hallmarks aging, it remains only vaguely defined. Its core feature embraces defects in energy-producing molecular machinery, respiratory complexes (MRCs). The causes and consequences these hold research attention. In this review, we assess lifecycle complexes, from biogenesis to degradation, look closely at mechanisms that could underpin their aged cells. We discuss how processes be altered by aging expand on fate MRCs age-associated pathologies. Given complexity behind MRC maintenance functionality, several traits contribute phenomenon known as dysfunction. New advances will help us better understand machinery age-related diseases.

Language: Английский

Citations

0
The Roles of White Adipose Tissue and Liver NADPH in Dietary Restriction-Induced Longevity DOI Creative Commons

Leah E. Jamerson,

Patrick C. Bradshaw

Antioxidants, Journal Year: 2024, Volume and Issue: 13(7), P. 820 - 820

Published: July 8, 2024

Dietary restriction (DR) protocols frequently employ intermittent fasting. Following a period of fasting, meal consumption increases lipogenic gene expression, including that NADPH-generating enzymes fuel lipogenesis in white adipose tissue (WAT) through the induction transcriptional regulators SREBP-1c and CHREBP. knockout mice, unlike controls, did not show an extended lifespan on DR diet. WAT cytoplasmic NADPH is generated by both malic enzyme 1 (ME1) pentose phosphate pathway (PPP), while liver primarily synthesized folate cycle provided one-carbon units serine catabolism. During daily fasting diet, fatty acids are released from transported to peripheral tissues, where they used for beta-oxidation phospholipid lipid droplet synthesis, monounsaturated (MUFAs) may activate Nrf1 inhibit ferroptosis promote longevity. Decreased PPP stimulated browning protected high-fat high levels macrophages linked obesity. But oscillations [NADPH]/[NADP+] feeding cycles play important role maintaining metabolic plasticity drive Studies measuring malate/pyruvate as proxy [NADPH]/[NADP+], well studies using fluorescent biosensors expressed animal models monitor changes needed during ad libitum diets determine associated with

Language: Английский

Citations

3
Mitochondria in skeletal system-related diseases DOI Open Access

Liang Pei,

Zizhen Yao, Liang Dong

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 181, P. 117505 - 117505

Published: Nov. 4, 2024

Language: Английский

Citations

1
The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain DOI Creative Commons

Jule Gerlach,

Paola Pireddu,

Xiaoqun Zhang

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 14, 2024

Abstract The highly conserved CHCHD2 and CHCHD10 are small mitochondrial proteins residing in the intermembrane space. Recently, mutations genes have been linked to severe disorders, including Parkinson’s disease amyotrophic lateral sclerosis. In cultured cells, a fraction of oligomerize form high molecular weight complex unknown function. Here, we generated whole-body Chchd2 knockout mouse investigate vivo role its protein complex. We show that is crucial for sustaining full motor capacity, normal striatal dopamine levels, lipid homeostasis brain adult male mice. also demonstrate tissues, exist exclusively as complex, whose levels finely tuned under physiological conditions. response dysfunction, abundance size CHCHD2-CHCHD10 increases, mechanism across different tissues. Although loss does not abolish oligomerization, it enhances cell vulnerability stress, suggesting protective against damage. Our findings uncover preserving tissue provide important insights into involvement human diseases.

Language: Английский

Citations

0