Puigserver Lab

Endurance Bio ready for Phase 2 trials of drug targeting ‘master regulator’ of cell energy metabolism.

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#longevity #biotech #Parkinsons #mitochondria #PGC1α 

❤️Our October issue is out❤️Read about the RNA editing enzyme ADAR1 regulating atherosclerosis progression, PGC-1α and cardiac adaptation to exercise training, the role of LYVE1-macrophages in heart regeneration and peripheral artery disease, and more.

Check out the article overview of Dr. Rosenzweig's latest publication "Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α":

Skeletal Muscle PGC‐1α Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis Background The coupling of oxygen consumption to ATP synthesis via oxidative phosphorylation (OXPHOS) is central for cellular energy homeostasis. Some studies suggest exercise training increases the.....

Skeletal Muscle PGC-1α Remodels Mitochondrial Phospholipidome but Does Not Alter Energy Efficiency for ATP Synthesis
onlinelibrary.wiley.com/doi/10.1002/...

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α | Nature Cardiovascular Research Endurance exercise promotes adaptive growth and improved function of myocytes, which is supported by increased mitochondrial activity. In skeletal muscle, these benefits are in part transcriptionally coordinated by peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). The importance of PGC-1α to exercise-induced adaptations in the heart has been unclear. Here we show that deleting PGC-1α specifically in cardiomyocytes prevents the expected benefits from exercise training and instead leads to heart failure after just 6 weeks of training. Consistent with this, in humans, rare genetic variants in PPARGC1A, which encodes PGC-1α, are associated with increased risk of heart failure. In this model, we identify growth differentiation factor 15 (GDF15) as a key heart-secreted mediator that contributes to this dysfunction. Blocking cardiac Gdf15 expression improves cardiac performance and exercise capacity in these mice. Finally, in human heart tissue, lower cardiomyocyt

Endurance exercise boosts heart health via PGC-1α, suppressing GDF15. Without PGC-1α in heart cells, benefits drop! #CardiacScience PMID:40993371, Nat Cardiovasc Res 2025 @broadinstitute https://doi.org/10.1038/s44161-025-00712-3 #Medsky #Pharmsky #RNA #ASHG #ESHG 🧪

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α - Nature Cardiovascular Research Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α
www.nature.com/articles/s44...

Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α - Nature Cardiovascular Research Khetarpal et al. show that the metabolic regulator PGC-1α is essential in heart muscle cells for exercise-driven cardiac growth, and that suppression of the stress-induced myokine GDF15 is required to enable cardiomyocyte adaptations to training.

Dr. Rosenzweig recently had an article published in Natured Cardiovascular Research: "Cardiac adaptation to endurance exercise training requires suppression of GDF15 via PGC-1α."

Read the article here: www.nature.com/articles/s44...

Sex difference in BAT thermogenesis depends on PGC-1α–mediated phospholipid synthesis in mice - Nature Communications Brown adipose tissue (BAT) plays a role in energy expenditure but its thermogenic activities differ between sexes. Here, the authors show that PGC-1α enhances mitochondrial function and BAT thermogene...

PGC-1α–mediated phospholipid synthesis plays a pivotal role in BAT thermogenesis in a sex-dependent manner in mice revealing a new therapeutic target for metabolic diseases in postmenopausal women. www.nature.com/articles/s41...

Thanks, Tom and Jonathan!
‪@danafarber.bsky.social‬
‪@harvardcellbio.bsky.social‬

New preview just published in Molecular Cell! We highlight exciting work by Chen et al. identifying an arginine sensing axis mediated by BAG2 and SAMD4B that promotes survival under arginine deficiency.

t.co/m71gz29mUv

Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia - Nature Cancer Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

📢Article now online at Nature Cancer!

'Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia'

✏️By Young-Mee Kim, Jalees Rehman and colleagues

🔗 www.nature.com/articles/s43...

Skeletal muscle endothelial dysfunction through the activin A–PGC1α axis drives progression of cancer cachexia - Nature Cancer Using multiple in vivo mouse models, Rehman and colleagues report that tumor-induced impairments in the muscle vasculature mediated by circulating activin A contribute to cachexia development during c...

A vascular perspective on #cancer cachexia here restoring endothelial PGC1α activity preserved vascular density and muscle mass in tumor-bearing mice @natcancer.nature.com www.nature.com/articles/s43...

RBM43 controls PGC1α translation and a PGC1α-STING signaling axis Dumesic et al. identify RBM43 as an RNA-binding protein that governs mitochondrial biogenesis through suppression of PGC1α translation. RBM43 is induced by inflammatory signaling and controls a diabetogenic regulatory axis in adipocytes whereby decreased…

Online now: RBM43 controls PGC1α translation and a PGC1α-STING signaling axis

SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO - Nature Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted canc...

(1/3) Excited to share our latest work using
@depmap.org to uncover a new synthetic lethality in two distinct patient populations!

We found that SKI complex inactivation through two independent genomic alterations creates a dependency on PELO

#CancerResearch #SyntheticLethality #Genomics #DepMap

SKI complex loss renders 9p21.3-deleted or MSI-H cancers dependent on PELO - Nature Analysis of large-scale CRISPR screening data, combined with experiments in patient-derived tumour organoid models, identifies PELO as a potential therapeutic target in chromosomal 9p21.3-deleted canc...

Exciting new synthetic lethal target emerging from #depmap data 🧪🧬

Frequent passenger mutations in genes involved in mRNA quality control lead to a dependency on PELO-HBS1L

Congratulations to the DepMap team! @vazquezf.bsky.social
#depmap #cancertarget #syntheticlethal

@danafarber.bsky.social @harvardcellbio.bsky.social @danafarbernews.bsky.social

Chaperone-mediated insertion of mitochondrial import receptor TOM70 protects against diet-induced obesity - Nature Cell Biology Latorre-Muro et al. show that the cytosolic chaperone PPID drives insertion of the mitochondrial import receptor TOM70 into the mitochondrial outer membrane, thereby regulating body temperature, gluco...

💫NEW by @ppuigserverb.bsky.social & co: the chaperone PPID drives insertion of the #mitochondria import receptor TOM70 into the mitochondrial outer membrane, regulating body temperature, glucose homeostasis and body weight in #obese mice.
👉https://rdcu.be/d8atv
www.nature.com/articles/s41...

We are looking for candidates with backgrounds in immunology, ideally with experience in multicolor FACS and single cell methods to complement our deep knowledge of cancer metabolism. More information about us can be found on our website: puigserver.dfci.harvard.edu (2/2)

We are hiring! After the publication of our last paper, our lab has openings for #postdoc fellows in projects looking at the interactions between tumor metabolism and immunology. Direct inquiries to pere_puigserver@dfci.harvard.edu. Please share! (1/2)

Very exciting findings @ppuigserverb.bsky.social connect mitochondrial ETC deficiencies with cancer cell immunogenicity expanding the repertoire of strategies to target tumor vulnerabilities

@ppuigserverb.bsky.social‬ @danafarber.bsky.social @harvardcellbio.bsky.social

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity - Nature Cancer Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of ...

Online now!

Puigserver and team show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of antigen-processing and presentation components.

👇
www.nature.com/articles/s43...

Really cool work from @ppuigserverb.bsky.social lab! Further strengthening the emerging links between perturbed bioenergetics and effectiveness of immunotherapy 👌👍

#mitochondria #cancer #keto

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity - Nature Cancer Puigserver and colleagues show that genetic targeting of specific mitochondrial respiratory complex I subunits in melanoma and breast cancer cells boosts tumor immune surveillance via upregulation of ...

Selective deficiency of mitochondrial respiratory complex I subunits Ndufs4/6 causes tumor immunogenicity
www.nature.com/articles/s43...
@ppuigserverb.bsky.social @naturecancer.bsky.social
www.nature.com/articles/s43...

Thanks!

Thanks, HaGe!

Thanks Payam!

Thanks for the News!

Thanks Christian!