bims-raghud 2024-12-15 papers

Issue of 2024–12–15
three papers selected by
Irene Sambri, TIGEM

Kidney Dis (Basel). 2024 Dec;10(6): 573-587

Xiaolu Fan, Linlin Wu, Fengqi Wang, Dong Liu, Xufeng Cen, Hongguang Xia.

Background: Mitophagy is a crucial process involved in maintaining cellular homeostasis by selectively eliminating damaged or surplus mitochondria. As the kidney is an organ with a high dynamic metabolic rate and abundant mitochondria, it is particularly crucial to control mitochondrial quality through mitophagy. Dysregulation of mitophagy has been associated with various renal diseases, including acute and chronic kidney diseases, and therefore a better understanding of the links between mitophagy and these diseases may present new opportunities for therapeutic interventions.
Summary: Mitophagy plays a pivotal role in the development of kidney diseases. Upregulation and downregulation of mitophagy have been observed in various kidney diseases, such as renal ischemia-reperfusion injury, contrast-induced acute kidney injury, diabetic nephropathy, kidney fibrosis, and several inherited renal diseases. A growing body of research has suggested that PINK1 and Parkin, the main mitophagy regulatory proteins, represent promising potential therapeutic targets for kidney diseases. In this review, we summarize the latest insights into how the progression of renal diseases can be mitigated through the regulation of mitophagy, while highlighting their performance in clinical trials.
Key Message: This review comprehensively outlines the mechanisms of mitophagy and its role in numerous kidney diseases. While early research holds promise, most mitophagy-centered therapeutic approaches have yet to reach the clinical application stage.

Keywords: Acute kidney injury; Alport syndrome; Chronic kidney disease; Mitophagy; Parkin

DOI: https://doi.org/10.1159/000541486

Front Immunol. 2024 ;15 1506426

Beclin-1: a therapeutic target at the intersection of autophagy, immunotherapy, and cancer treatment.

Zhumin Cao, Ke Tian, Yincheng Ran, Haonan Zhou, Lei Zhou, Yana Ding, Xiaowei Tang.

The significant identification of Beclin-1's function in regulating autophagy flow signified a significant progression in our understanding of cellular operations. Beclin-1 acts as a scaffold for forming the PI3KC3 complex, controlling autophagy and cellular trafficking processes in a complicated way. This intricate protein has garnered considerable attention due to its substantial impact on the development of tumors. Strong evidence indicates Beclin-1 plays a critical role in controlling autophagy in various human cancer types and its intricate connection with apoptosis and ferroptosis. The potential of Beclin-1 as a viable target for cancer therapy is highlighted by its associations with key autophagy regulators such as AMPK, mTOR, and ATGs. Beclin-1 controls the growth and dissemination of tumors by autophagy. It also affects how tumors react to therapies such as chemotherapy and radiation therapy. The role of Beclin-1 in autophagy can influence apoptosis, depending on whether it supports cell survival or leads to cell death. Beclin-1 plays a crucial role in ferroptosis by increasing ATG5 levels, which in turn promotes autophagy-triggered ferroptosis. Finally, we analyzed the possible function of Beclin-1 in tumor immunology and drug sensitivity in cancers. In general, Beclin-1 has a significant impact on regulating autophagy, offering various potentials for medical intervention and altering our understanding of cancer biology.

Keywords: Beclin-1; apoptosis and ferroptosis; autophagy; autophagy flux; immunotherapy; mTOR

DOI: https://doi.org/10.3389/fimmu.2024.1506426

Nefrologia (Engl Ed). 2024 Dec 06. pii: S2013-2514(24)00210-4. [Epub ahead of print]

Cardiovascular-kidney-metabolic syndrome definition and its role in the prevention, risk staging, and treatment. An opportunity for the Nephrology.

Aleix Cases, Jose Jesus Broseta, Maria Marqués, Secundino Cigarrán, Juan Carlos Julián, Roberto Alcázar, Alberto Ortiz.

The recent conceptualization of the cardiovascular-kidney-metabolic (CKM) syndrome by the American Heart Association (AHA) opens an opportunity for a multidisciplinary and lifelong approach in the risk stratification, early prevention, and treatment of the vicious circle generated by the interaction of cardiovascular, renal and metabolic risk factors and aggravated by the development of cardiovascular diseases (including their full spectrum: heart failure, atrial fibrillation, coronary heart disease, stroke, and peripheral arterial disease), chronic kidney disease or type 2 diabetes mellitus, with the excess or dysfunctional adiposity as the trigger. Three publications offer the rational basis of a conceptual decalogue and action plan and a new cardiovascular risk stratification equation since the age of 30 that includes measures of renal function/damage, among others, to promote effective cardiovascular, renal, and metabolic prevention. In Spain, we must leverage this momentum to adapt these new concepts to our reality with greater and improved collaboration between primary care and the specialties involved in CKM syndrome, including the formation of multidisciplinary units for the optimal management using a patient-centred approach.

Keywords: Cardiovascular disease; Chronic kidney disease; Diabetes; Enfermedad cardiovascular; Enfermedad renal crónica; Metabolic syndrome; Obesidad; Obesity; Síndrome metabólico

DOI: https://doi.org/10.1016/j.nefroe.2024.11.011