Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration

Pollard, Amelia K.; Shephard, Freya; Freed, John B.; Liddell, Susan; Chakrabarti, Lisa

doi:10.18632/aging.101064

Cited by 39 publications

(59 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our data show that enriched mitochondrial fractions have characteristic lipidomic profiles specific to the age and type of tissue, echoing our findings in the mitochondrial proteome [43]. We find the brain mitochondrial lipidome is highly modulated with ageing, with fatty acids decreased in older animals.…”

Section: Discussionsupporting

confidence: 89%

Mouse mitochondrial lipid composition is defined by age in brain and muscle

Pollard

Ortori

Stöger

et al. 2017

Aging

Self Cite

View full text Add to dashboard Cite

Functionality of the lipid rich mitochondrial organelle declines with increased age. Recent advances in lipidomic technologies allowed us to perform a global characterisation of lipid composition in two different tissue types and age ranges. Ultra-high performance liquid chromatography coupled with high resolution mass spectrometry was used to establish and compare mitochondrial lipidomes of brain and skeletal muscle from young (4-11 weeks old) and middle age (78 weeks old) healthy mice. In middle age the brain mitochondria had reduced levels of fatty acids, particularly polyunsaturated fatty acids, while skeletal muscle mitochondria had a decreased abundance of phosphatidylethanolamine, but a pronounced increase of triglyceride levels. Reduced levels of phosphatidylethanolamines are known to decrease mitochondrial membrane fluidity and are connected with accelerated ageing. In mitochondria from skeletal muscle we propose that increased age causes a metabolic shift in the conversion of diacylglycerol so that triglycerides predominate compared with phosphatidylethanolamines. This is the first time mitochondrial lipid content in normal healthy mammalian ageing brain and muscle has been catalogued in such detail across all lipid classes. We identify distinct mitochondrial lipid signatures that change with age, revealing tissue-specific lipid pathways as possible targets to ameliorate ageing-related mitochondrial decline.

show abstract

Section: Discussionsupporting

confidence: 89%

Mouse mitochondrial lipid composition is defined by age in brain and muscle

Pollard

Ortori

Stöger

et al. 2017

Aging

Self Cite

View full text Add to dashboard Cite

show abstract

“…Promising studies in transgenic mouse models of amyloidosis are currently ongoing in our laboratory. The physiological relevance of this approach is further highlighted by recent proteomic studies showing increased CAII in the mitochondria in aging and neurodegeneration (Pollard et al., 2016), as well as by our group's recent findings demonstrating the presence of multiple CA enzymes in amyloid plaques within the AD human brain (Drummond et al., 2017). …”

Section: Discussionmentioning

confidence: 58%

“…CA‐VA and CA‐VB have a mitochondrial localization (Ghandour, Parkkila, Parkkila, Waheed & Sly, 2000). CA‐II, known as cytoplasmic, was also recently shown by proteomic profiling to be increased in brain mitochondria in aging and neurodegeneration (Pollard, Shephard, Freed, Liddell & Chakrabarti, 2016). CA inhibitors (CAIs) are used to treat a variety of disorders including glaucoma, epilepsy, neuropsychiatric disorders, and acute mountain sickness (Aggarwal, Kondeti & McKenna, 2013; Fossati et al., 2016; Huang et al., 2010).…”

Section: Introductionmentioning

confidence: 97%

Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity

et al. 2018

View full text Add to dashboard Cite

SummaryMounting evidence suggests that mitochondrial dysfunction plays a causal role in the etiology and progression of Alzheimer's disease (AD). We recently showed that the carbonic anhydrase inhibitor (CAI) methazolamide (MTZ) prevents amyloid β (Aβ)‐mediated onset of apoptosis in the mouse brain. In this study, we used MTZ and, for the first time, the analog CAI acetazolamide (ATZ) in neuronal and cerebral vascular cells challenged with Aβ, to clarify their protective effects and mitochondrial molecular mechanism of action. The CAIs selectively inhibited mitochondrial dysfunction pathways induced by Aβ, without affecting metabolic function. ATZ was effective at concentrations 10 times lower than MTZ. Both MTZ and ATZ prevented mitochondrial membrane depolarization and H2O2 generation, with no effects on intracellular pH or ATP production. Importantly, the drugs did not primarily affect calcium homeostasis. This work suggests a new role for carbonic anhydrases (CAs) in the Aβ‐induced mitochondrial toxicity associated with AD and cerebral amyloid angiopathy (CAA), and paves the way to AD clinical trials for CAIs, FDA‐approved drugs with a well‐known profile of brain delivery.

show abstract

“…In addition, the addition of recombinant CA9 enzyme promoted wound re-epithelialization [40]. Furthermore, a proteome study also revealed the involvement of CA2 protein in aging and neurodegeneration in a mouse [41]. Here, we demonstrated that LACCE promoted the regeneration of human keratinocyte cells by up-regulating CA2 expression.…”

Section: Discussionmentioning

confidence: 65%

Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract through Transcriptome Profiling

Cho

Kim²,

Kim³

et al. 2020

Genes

View full text Add to dashboard Cite

Edelweiss (Leontopodium Alpinum) in the family Asteraceae is a wildflower that grows in rocky limestone places. Here, we investigated the efficacy of edelweiss callus culture extract (Leontopodium Alpinum callus culture extract; LACCE) using multiple assays from in vitro to in vivo as well as transcriptome profiling. Several in vitro assay results showed the strong antioxidant activity of LACCE in response to UVB treatment. Moreover, LACCE suppressed inflammation and wrinkling; however, moisturizing activity was increased by LACCE. The clinical test in vivo demonstrated that constant application of LACCE on the face and skin tissues improved anti-periorbital wrinkles, skin elasticity, dermal density, and skin thickness compared with the placebo. The RNA-Sequencing results showed at least 16.56% of human genes were expressed in keratinocyte cells. LACCE up-regulated genes encoding several KRT proteins; DDIT4, BNIP3, and IGFBP3 were involved in the positive regulation of the developmental process, programmed cell death, keratinization, and cornification forming skin barriers, which provide many advantages in the human skin. By contrast, down-regulated genes were stress-responsive genes, including metal, oxidation, wounding, hypoxia, and virus infection, suggesting LACCE did not cause any harmful stress on the skin. Our comprehensive study demonstrated LACCE is a promising agent for anti-aging cosmetics.

show abstract

Mitochondrial proteomic profiling reveals increased carbonic anhydrase II in aging and neurodegeneration

Cited by 39 publications

References 47 publications

Mouse mitochondrial lipid composition is defined by age in brain and muscle

Mouse mitochondrial lipid composition is defined by age in brain and muscle

Carbonic anhydrase inhibition selectively prevents amyloid β neurovascular mitochondrial toxicity

Anti-Aging Effects of Leontopodium alpinum (Edelweiss) Callus Culture Extract through Transcriptome Profiling

Contact Info

Product

Resources

About