Five women standing outdoors with trees in the background.

Minerva Fast Track Group Guhathakurta

Epimetabolism: Mechanisms of metabolic and epigenetic control of cell fate decision

Epigenetic regulators, including chromatin remodelers and histone-modifying enzymes, play critical roles in the transcriptional regulation of gene expression that underlies cellular fate decisions. Mitochondria, the central metabolic hub of the cell, produce key metabolites required for epigenetic modifications while also functioning as signaling organelles that integrate intra- and intercellular cues and relay them to the nucleus. Our research investigates the molecular mechanisms underlying nucleus-mitochondria crosstalk and how this bidirectional communication coordinates epigenetic regulation and metabolic homeostasis to govern cell fate decisions during healthy development.

Mission

Our mission is to understand how metabolic, mitochondrial, hormonal, and epigenetic signals interact to shape brain development, cell fate, and healthy ageing.

Goals

Our research aims to:

Elucidate how metabolic and mitochondrial signaling is integrated into the epigenetic landscape to direct neural stem cell fate decisions during neurodevelopment.
Understand how metabolism, epigenetics, and hormonal signaling influence cell identity, metabolic programming, and neuron-glia interactions.
Identify the molecular mechanisms by which dysregulation of these pathways contributes to neurodevelopmental disorders, brain ageing and age-associated neurodegenerative diseases.

Impact

By uncovering the fundamental mechanisms linking metabolism, mitochondrial function, epigenetic regulation and hormone signaling, our research seeks to advance our understanding of human brain development and resilience. These discoveries have the potential to reveal new mechanisms underlying neurodevelopmental disorders as well as age-related neurodegenerative diseases. Ultimately, our work aims to inform disease prevention strategies, improve nutritional and metabolic interventions, and identify novel therapeutic targets that promote lifelong brain health and healthy ageing.

The group is embedded within the Department of Chromatin Regulation led by Asifa Akhtar.

Selected publications

Erdogdu NU, Guhathakurta S, Oellers R, Shvedunova M, Morin JA, Patrick EM, Seyfferth J, Deboutte W, Gomez-Auli A, Mittler G, Cissé II, Akhtar A (2026):

Histone acetylation-dependent clustering of BRD2 instructs transcription dynamics

Nature Genetics 58, 854-868.

Source

DOI

Guhathakurta S, Erdogdu NU, Hoffmann JJ, Grzadzielewska I, Schendzielorz A, Seyfferth J, Mårtensson CU, Corrado M, Karoutas A, Warscheid B, Pfanner N, Becker T & Asifa Akhtar (2023)

COX17 acetylation via MOF–KANSL complex promotes mitochondrial integrity and function

Nature Metabolism 5, 1931-1952.

Featured in News & Views by Natalie Niemi (Nature Metabolism) and by Dimitris Typas (Nature Structural and Molecular Biology).

Source

DOI

Sheikh BN, Guhathakurta S, Tsang TH, Schwabenland M, Renschler G, Herquel B, Bhardwaj V, Holz H, Stehle T, Bondareva O, Aizarani N, Mossad O, Kretz O, Reichardt W, Chatterjee A, Braun LJ, Thevenon J, Sartelet H, Blank T, Grün D, von Elverfeldt D, Huber TB, Vestweber D, Avilov S, Prinz M, Buescher JM and Akhtar A (2020)

Neural metabolic imbalance induced by MOF dysfunction triggers pericyte activation and breakdown of vasculature

Nature Cell Biology 22, 828-84.

Source

DOI

Karoutas A, Szymanski W, Rausch T, Guhathakurta S, Rog-Zielinska EA, Peyronnet R, Seyfferth J, Chen HR, de Leeuw R, Herquel B, Kimura H, Mittler G, Kohl P, Medalia O, Korbel JO, Asifa Akhtar (2019)

The NSL complex maintains nuclear architecture stability via Lamin A/C acetylation

Nature Cell Biology 21, 1248–1260.

Featured in News & Views (Nature Cell Biology) by Varvara V. Papova & Jerry L. Workman.

Source

DOI

Sheikh BN*, Guhathakurta S*, & Akhtar A (2019)

The non-specific lethal (NSL) complex at the crossroads of transcriptional control and cellular homeostasis.

EMBO Reports 20(7):e47630

* Equal contribution

Source

DOI

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