bims-mignad 2025-06-29 papers

Issue of 2025–06–29
three papers selected by
Melisa Emel Ermert, Amsterdam UMC

Biogerontology. 2025 Jun 23. 26(4): 124

Biological properties, synthetic pathways and anti-aging mechanisms of nicotinamide mononucleotide (NMN): Research progress and challenges.

Enhui Wang, Yuting Wang, Zhaofeng Zhang, Yanfei Jiang, Chunyue Zhao.

The increasing global population aging has made the prevention and control of aging-related diseases a major public health challenge in the twenty-first century. Nicotinamide mononucleotide (NMN), as a precursor of nicotinamide adenine dinucleotide (NAD+), has garnered significant attention in recent years for its anti-aging potential. This review comprehensively reviews the metabolic pathways and molecular mechanisms of NMN, comparing the technical characteristics and industrialization prospects of chemical synthesis, microbial fermentation, and enzyme-catalyzed synthesis. The molecular targets and networks of NMN in core aging mechanisms, such as DNA damage repair, mitochondrial function regulation, inflammatory response balance, gut microbiota remodeling, and autophagy pathway activation, are analyzed. The molecular mechanism of NMN in slowing down the aging process through multi-target synergistic effects is elucidated. However, critical issues such as age-stratified dosage modeling, long-term safety, and efficacy of NMN still require in-depth research. This review provides a theoretical basis and research direction for translational research and precise anti-aging strategies of NMN.

Keywords: Anti-aging; Autophagy; Chemical/biological synthesis; Gut microbiota; Nicotinamide adenine dinucleotide; Nicotinamide mononucleotide

DOI: https://doi.org/10.1007/s10522-025-10270-7

Mol Cell. 2025 Jun 24. pii: S1097-2765(25)00507-6. [Epub ahead of print]

An NADH-controlled gatekeeper of ATP synthase.

Fabian Schildhauer, Petra S J Ryl, Simon M Lauer, Swantje Lenz, Ayşe Berçin Barlas, Vasileios R Ouzounidis, Kate Jeffrey, Daniel-Cosmin Marcu, Francis J O'Reilly, Andrea Graziadei, Marchel Stuiver, Kita Schmidt, Helge Ewers, Christian M T Spahn, Ezgi Karaca, Karl Emanuel Busch, Dhanya Cheerambathur, David Schwefel, Juri Rappsilber.

ATP fuels crucial cellular processes and is obtained mostly by oxidative phosphorylation (OXPHOS) at the inner mitochondrial membrane. While significant progress has been made in mechanistic understanding of ATP production, critical aspects surrounding its substrate supply logistics are poorly understood. We identify an interaction between mitochondrial apoptosis-inducing factor 1 (AIFM1) and adenylate kinase 2 (AK2) as gatekeeper of ATP synthase. This interaction is NADH dependent and influenced by glycolysis, linking it to the cell's metabolic state. Genetic interference with AIFM1/AK2 association impedes the ability of Caenorhabditis elegans animals to handle altered metabolic rates and nutrient availability. Together, the results imply AIFM1 as a cellular NADH sensor, placing AK2 next to the OXPHOS complexes for local ADP regeneration as the substrate for ATP synthesis. This metabolic signal relay balances ATP synthase substrate supply against ATP conservation, enabling cells to adapt to fluctuating energy availability, with possible implications for AIFM1-related mitochondrial diseases.

Keywords: AIFM1; AK2; ATP synthesis; OXPHOS; adenylate kinase 2; apoptosis-inducing factor 1; cell signaling; crosslinking mass spectrometry; energy metabolism; mitochondria; mitochondrial; oxidative phosphorylation; protein structure; protein-protein interaction

DOI: https://doi.org/10.1016/j.molcel.2025.06.007

Free Radic Biol Med. 2025 Jun 19. pii: S0891-5849(25)00785-3. [Epub ahead of print]

Novel role of Peroxiredoxin 6 in Ferroptosis: Bridging selenium transport with enzymatic functions.

Debojyoti Pal, Santosh K Sandur.

Ferroptosis, an iron dependent mode of cell death, is characterized by oxidative damage to cell membrane by uncontrolled lipid peroxidation. Prevention of lipid peroxide formation or its rapid neutralization is critical to avert ferroptosis. Selenoproteins such as glutathione peroxidase 4 (GPX4) and thioredoxin reductase 1 (TXNRD1) are critical enzymes which prevent ferroptosis. Peroxiredoxin 6 (PRDX6) is a lipid peroxide specific peroxidase enzyme with moonlighting functions that affect ferroptosis sensitivity in a multitude of ways. Further, it has recently been discovered that PRDX6 also acts as an intracellular carrier of selenium, allowing efficient utilization of organic and inorganic sources of selenium for synthesis of selenoproteins. Thus, PRDX6 can affect abundance and functionality of anti-ferroptotic selenoproteins GPX4 and TXNRD1. This review is focussed on understanding the different functions of PRDX6 in ferroptosis in light of its newly discovered role in selenoprotein synthesis.

DOI: https://doi.org/10.1016/j.freeradbiomed.2025.06.036