bims-smemid 2025-07-06 papers

Nature. 2025 Jul 01.

Publisher Correction: Metabolic adaptations direct cell fate during tissue regeneration.

Almudena Chaves-Perez, Scott E Millman, Sudha Janaki-Raman, Yu-Jui Ho, Clemens Hinterleitner, Valentin J A Barthet, John P Morris, Francisco M Barriga, Jose Reyes, Aye Kyaw, H Amalia Pasolli, Dana Pe'er, Craig B Thompson, Lydia W S Finley, Justin R Cross, Scott W Lowe.

DOI: https://doi.org/10.1038/s41586-025-09294-3

Biol Chem. 2025 Jul 07.

Stress response pathways: machineries and mechanisms.

Johannes Buchner, Johannes M Herrmann.

DOI: https://doi.org/10.1515/hsz-2025-0168

Nat Commun. 2025 Jul 01. 16(1): 5465

Mitophagy mitigates mitochondrial fatty acid β-oxidation deficient cardiomyopathy.

Nuo Sun, Hayley Barta, Samhita Chaudhuri, Kangxuan Chen, Jiacheng Jin, Hongke Luo, Mingchong Yang, Judith Krigman, Ruohan Zhang, Shridhar Sanghvi, Shiori Sekine, Hannah Sanders, Dominic Kolonay, Mudra Patel, Kedryn Baskin, Harpreet Singh, Pengyi Zhang, Gang Xin, Toren Finkel.

The healthy heart relies on mitochondrial fatty acid β-oxidation (FAO) to sustain its high energy demands. FAO deficiencies can cause muscle weakness, cardiomyopathy, and, in severe cases, neonatal/infantile mortality. Although FAO deficits are thought to induce mitochondrial stress and activate mitophagy, a quality control mechanism that eliminates damaged mitochondria, the mechanistic link in the heart remains unclear. Here we show that mitophagy is unexpectedly suppressed in FAO-deficient hearts despite pronounced mitochondrial stress, using a cardiomyocyte-specific carnitine palmitoyltransferase 2 (CPT2) knockout model. Multi-omics profiling reveals impaired PINK1/Parkin signaling and dysregulation of PARL, a mitochondrial protease essential for PINK1 processing. Strikingly, deletion of USP30, a mitochondrial deubiquitinase that antagonizes PINK1/Parkin function, restores mitophagy, improves cardiac function, and significantly extends survival in FAO-deficient animals. These findings redefine the mitophagy response in FAO-deficient hearts and establish USP30 as a promising therapeutic target for metabolic cardiomyopathies and broader heart failure characterized by impaired FAO.

DOI: https://doi.org/10.1038/s41467-025-60670-z

npj metabolic health and disease... 2025 Jun 18. 3(1): 26

The role of NAD+ metabolism and its modulation of mitochondria in aging and disease.

Khalishah Yusri, Sandra Jose, Karen S Vermeulen, Trina Chia Min Tan, Vincenzo Sorrentino.

Nicotinamide adenine dinucleotide (NAD+) is a coenzyme involved in a plethora of physiological reactions, with a key relevance in supporting mitochondrial function. Due to its critical role in these cellular processes, declining levels of NAD+ are associated with general aging and chronic disorders, including cognitive decline, sarcopenia, and metabolic diseases. These conditions are also typified by loss of mitochondrial health through dysfunction of homeostatic components such as mitophagy, unfolded protein response, and the antioxidant system. Therefore, raising cellular NAD+ through vitamin B3 family precursors or via drug-based interventions has become a broadly used strategy to restore mitochondrial and organismal homeostasis, with NAD+ precursors becoming a popular supplementation approach. As increasing components of the NAD+ biology are unraveled, this comprehensive review summarizes the advances in mechanisms of NAD+ metabolism and its modulation via compound-based strategies. Furthermore, it highlights the role of NAD+ in mitochondrial homeostasis in aging and disease conditions, the latest results of NAD+-boosting therapeutics in clinical trials, and areas of further translational development.

DOI: https://doi.org/10.1038/s44324-025-00067-0