bims-raghud 2026-03-08 papers

Issue of 2026–03–08
three papers selected by
Irene Sambri, TIGEM

Nephrology (Carlton). 2026 Mar;31(3): e70177

Multicystic Kidney Disease in a Family With Tuberous Sclerosis Complex.

Julia S Donald, Caitlin Edmonstone, Denise L Chan, Clara W T Chung, Sean E Kennedy.

Tuberous sclerosis complex (TSC) is a multisystem condition associated with disease-causing variants of either TSC1 or TSC2 genes. Significant kidney involvement in TSC is most often due to development of angiomyolipomas (AMLs) and occurs more frequently in people with TSC2 variants. Kidney cysts are also commonly seen; however, these are usually small and not recognised as problematic. A subset of patients has a severe polycystic kidney disease due to a contiguous gene deletion involving PKD1 and TSC2 on chromosome 16. End-stage kidney disease (ESKD) occurs commonly in patients with TSC2/PKD1 deletions but is otherwise rare. We report a family with a TSC1 variant. The father, a 34-year-old male, presented with chronic kidney disease with eGFR 31 mL/min, proteinuria 1.2 g/day and hypertension. Ultrasound showed small cystic kidneys. Coincidentally, his 2-year-old daughter presented with seizures and had skin lesions and neurological signs consistent with TSC. Her 1-year-old brother also met TSC diagnostic criteria. Further investigations of the father showed typical skin lesions and cerebral tubers. Genetic testing identified a variant in TSC1. The father progressed to ESKD and subsequently received a kidney transplant. His two children have similar renal ultrasounds with multiple cysts; now aged 18 and 16 years, they have normal eGFR and no proteinuria. This family manifests a rarely described multicystic phenotype and TSC1 variant. The father's case demonstrates the risk of progressive kidney disease in TSC, even in the absence of AMLs or TSC2/PKD1 contiguous deletion, and highlights the importance of renal monitoring of all adults with TSC.

DOI: https://doi.org/10.1111/nep.70177

J Cardiovasc Transl Res. 2026 Mar 06. pii: 34. [Epub ahead of print]19(1):

Mitochondrial Resilience: Unraveling the Triadic Interplay of Phosphocreatine, Cyclophilin D, and STAT3 in Heart Failure.

Eskandar Qaed, Wu Liu, Waleed Aldahmash, Mueataz A Mahyoub, Haya A Elshafei, Zeyao Tang.

Heart failure remains a major global health burden, with mitochondrial dysfunction recognized as a key contributor to its onset and progression. This review highlights three critical regulators of mitochondrial integrity phosphocreatine (PCr), cyclophilin D (CypD), and signal transducer and activator of transcription 3 (STAT3) and their coordinated roles in cardiac function. PCr is vital for sustaining myocardial energy balance, particularly under metabolic stress. CypD controls the mitochondrial permeability transition pore, regulating cell death pathways that contribute to cardiac injury. Beyond its classical nuclear actions, STAT3 supports mitochondrial respiration, biogenesis, and resistance to oxidative damage. Evidence reveals a functional interplay among these regulators, forming a protective network that preserves mitochondrial performance. Disruption of this network promotes energetic failure, mitochondrial injury, and heart failure progression. Targeting PCr metabolism, CypD activity, and STAT3 signaling may represent a promising therapeutic approach to enhance mitochondrial resilience and improve clinical outcomes in heart failure patients.

Keywords: Cyclophilin D; Heart failure; Mitochondrial; Phosphocreatine; STAT3

DOI: https://doi.org/10.1007/s12265-026-10756-w

Nat Struct Mol Biol. 2026 Mar 05.

Function and regulation of the mitochondrial stress response.

Joshua B Sheetz, Srividya Chandrasekhar, Michael Rapé.

As mitochondria have crucial roles in metabolism and signaling, their structure and function must be continuously monitored and rapidly adjusted to meet cellular demands. Critical to this regulation is a conserved stress response that detects and alleviates challenges to mitochondrial integrity. Recent work has shown that mitochondrial stress often elicits simultaneous protective reactions that act in a coordinated and tightly regulated fashion to preserve this essential organelle. Here we review components, coordination and control within this comprehensive stress response and discuss how increased understanding of mitochondrial stress signaling is beginning to inform therapeutic approaches directed against diseases of high unmet need.

DOI: https://doi.org/10.1038/s41594-026-01769-9