Metabolic biochemistry and bioenergetics. Coordinator: Fato

Fig. 1 Confocal microscopy assessment of mitophagy in control and mutant LIG3 fibroblasts. Panels represent merged images of CNT, 1-1, and 3-2, costained with MitoTracker Green and LysoTracker Red. Three visual fields in at least 3 independent samples per fibroblast type were analyzed. Scale bars: 20 μm.

Research themes

The biochemistry of metabolism and bioenergetics study the chemical processes that occur within cells to produce and utilize energy. Metabolism encompasses a set of biochemical reactions that convert nutrients into energy and fundamental molecules for life. Bioenergetics focuses on the mechanisms by which cells generate and store energy, primarily through mitochondrial oxidative phosphorylation and ATP production. Our research group is dedicated to studying the metabolic and bioenergetic processes, with the aim of gaining a deeper understanding of their molecular mechanisms and translating this knowledge into clinical applications for human health. The group’s work is structured around three main research themes:

1. Understanding Metabolic and Bioenergetic Mechanisms

Metabolic and bioenergetic processes are highly regulated to ensure energy balance and adaptation to environmental changes. A deeper understanding of these processes is crucial for elucidating the molecular basis of metabolic diseases, aging, neurodegenerative disorders, and cancer. Our studies focus on:

• Analyzing metabolic pathways and the interactions between metabolism and cellular signaling under both physiological and pathological conditions.
• Investigating the role of mitochondrial bioenergetics in the regulation of cellular homeostasis.
• Examining cellular metabolism in diseases such as diabetes, obesity, cancer, and neurodegeneration.

2. Study of the Effects of Plant-Derived Bioactive Compounds on Metabolism and Cellular Bioenergetics

Plant-derived bioactive molecules can modulate key biological processes such as metabolism, bioenergetics, inflammation, and oxidative stress, making them a field of growing interest in medicine and nutraceuticals. Understanding the molecular basis of their function is essential for the prevention and treatment of various diseases. Our research group aims to:

• Analyze the impact of plant compounds on the regulation of carbohydrate, lipid, and protein metabolism.
• Investigate the influence of these substances on ATP production, mitochondrial dynamics, and oxidative stress management.

Fig. 2: (h) Representative micrographs of control and e19 live fibroblasts stained with MitoTracker Green. (i) Morphology analysis performed with ImageJ MiNa plugin. Mutant fibroblasts displayed a perinuclear distribution of mitochondria with significantly shorter branch length in comparison with controls. At least three independent experiments were performed. Unpaired t-test with Welch's correction, *p = 0.0138 (means ± s.e.m.).

3. Redox Signaling and Cellular Homeostasis: NAD(P)H Oxidases (NOX), Aquaporins, Glucose Transport, and Their Role in Signal Transduction

Reactive species are not merely harmful byproducts; they act as intracellular messengers in various biological processes. Redox signaling and cellular homeostasis are closely interconnected and play a fundamental role in regulating metabolism, bioenergetics, and cell survival. Our research focuses on:

• Analyzing oxidative stress responses and studying the role of Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) in stimulating the production of antioxidant enzymes.
• Investigating the role of NADPH oxidases (NOX) in key processes such as cell proliferation and differentiation.

Lab Members

Romana Fato, Associate Professor

Christian Bergamini, Associate Professor

Cecilia Prata, Associate Professor

Nicola Rizzardi, Research Fellow (Post Doc)

Francesca Valenti, PhD Student

Luca Pincigher, PhD Student

Chiara Zalambani, PhD Student

Internship Projects 

Research line 1: two internship position each year

Research line 2: one internship positions each year

Research line 3: one internship positions each year

Main publications

• Diquigiovanni C, Rizzardi N, Cataldi-Stagetti E, Gozzellino L, Isidori F, Valenti F, Orsini A, Astolfi A, Giangregorio T, Pironi L, Boschetti E, Arrigo S, Maresca A, Magnoni P, Costanzini A, Carelli V, Taniguchi-Ikeda M, Fato R, Bergamini C, De Giorgio R, Bonora E. Glutamine Supplementation as a Novel Metabolic Therapeutic Strategy for LIG3-Dependent Chronic Intestinal Pseudo-Obstruction. 2025 Jan;168(1):68-83. doi: 10.1053/j.gastro.2024.08.009. Epub 2024 Aug 21. PMID: 39173721.
• Bergamini C, Leoni I, Rizzardi N, Melli M, Galvani G, Coada CA, Giovannini C, Monti E, Liparulo I, Valenti F, Ferracin M, Ravaioli M, Cescon M, Vasuri F, Piscaglia F, Negrini M, Stefanelli C, Fato R, Gramantieri L, Fornari F. “MiR-494 induces metabolic changes through G6pc targeting and modulates sorafenib response in hepatocellular carcinoma.” J Exp Clin Cancer Res. 2023 Jun 10;42(1):145. doi: 10.1186/s13046-023-02718-w. PMID: 37301960  PMCID: PMC10257313.
• Liparulo I, Bergamini C, Bortolus M, Calonghi N, Gasparre G, Kurelac I, Masin L, Rizzardi N, Rugolo M, Wang W, Aleo SJ, Kiwan A, Torri C, Zanna C, Fato R. Coenzyme Q biosynthesis inhibition induces HIF-1α stabilization and metabolic switch toward glycolysis. FEBS J. 2021 Mar;288(6):1956-1974. doi: 10.1111/febs.15561. Epub 2020 Sep 20. PMID: 32898935.
• Cervia D, Zecchini S, Pincigher L, Roux-Biejat P, Zalambani C, Catalani E, Arcari A, Del Quondam S, Brunetti K, Ottria R, Casati S, Vanetti C, Barbalace MC, Prata C, Malaguti M, Casati SR, Lociuro L, Giovarelli M, Mocciaro E, Falcone S, Fenizia C, Moscheni C, Hrelia S, De Palma C, Clementi E, Perrotta C. Oral administration of plumbagin is beneficial in in vivo models of Duchenne muscular dystrophy through control of redox signaling. Free Radic Biol Med. 2024 Nov 20;225:193-207. doi: 10.1016/j.freeradbiomed.2024.09.037. PMID: 39326684.
• Rizzardi N, Pezzolesi L, Samorì C, Senese F, Zalambani C, Pitacco W, Calonghi N, Bergamini C, Prata C, Fato R. Natural Astaxanthin Is a Green Antioxidant Able to Counteract Lipid Peroxidation and Ferroptotic Cell Death. Int J Mol Sci. 2022 Dec 1;23(23):15137. doi: 10.3390/ijms232315137. PMID: 36499464; PMCID: PMC9737268.