My research focuses on how mitochondria–ER contact sites (MERCS), BCL-2 family proteins, mitochondrial dynamics and regulated cell-death machineries cooperate to determine cell-fate transitions in neurodegeneration and cancer. Although these processes are known to be altered in disease, their mechanistic interplay within MERCS and the sequence of events that drive the transition from healthy to pathological states remain poorly defined (Larrañaga-SanMiguel A, TCB 2025). We envision MERCS as hubs integrating apoptotic stresses, BCL-2 proteins and metabolic and stress-adaptation pathways, acting as cellular “health meters”.

Building on this foundation, my laboratory investigates how MERCS regulate apoptotic signalling and maintain mitochondrial function across cellular states. We integrate biophysics, advanced imaging, mechanistic cell biology, proximity biotinylation and near-native MERCS extraction to define their composition, dynamics and functional organization. These approaches allow us to address how MERCS dysfunction contributes to early vulnerability in Alzheimer’s and Parkinson’s disease, and to identify MERCS modulators capable of restoring ER–mitochondria communication when these interfaces become compromised. Recent work includes the detection of early MERCS remodelling preceding mitochondrial dysfunction, MERCS-dependent mechanisms linking cell death sensitivity, and small molecules that restore ER–mitochondria apposition and improve cellular resilience to stress.

My scientific path began at the University of the Basque Country (EHU), where I completed a Bachelor’s in Biochemistry and Molecular Biology and a Master’s in Biomedicine. I pursued my PhD at the Biofisika Institutua (CSIC-EHU) under Dr. Gorka Basañez, investigating the membrane role of BCL-2 family proteins. We studied the membrane topology of the apoptotic effector BAX (Flores-Romero H. et al., Sci. Rep., 2017) and the cardiolipin-regulated pro-death activity of BFL1 (Flores-Romero H. et al., Cell Death Differ., 2019), mastering techniques and expertise in membrane biophysics, structural biology, cell biology and microscopy. For my postdoc, I moved to Prof. Ana García-Sáez’s group at IFIB (Uni. Tübingen) and CECAD (Uni. Cologne), expanding my work on BCL-2 proteins beyond apoptosis, studying their impact on metabolism, mitochondrial dynamics and MERCS biology. We showed that tBID, a protein belonging to the BCL-2 family, can replace canonical effectors directly inducing apoptosis in leukaemia models and this new permeabilization activity can modulate bacterial infection (Flores-Romero H. et al., EMBO J., 2021). Moreover, we found that MTCH2 can regulate BAX/BAK high order oligomerization, mitochondrial DNA release and inflammatory response. Another key focus of my postdoctoral work has been the characterization of MERCS. To study these structures, I developed advanced microscopy techniques and novel approaches, including the MERLIN biosensor, which is recognized for its speed, reliability, and versatility (Hertlein, V* and Flores-Romero H* et al, Life Sci.Alliance. 2019).

Together, these experiences have shaped a research program driven by a central goal: to decode how intracellular contact sites orchestrate cell-fate decisions and to turn this knowledge into new opportunities to counteract neurodegeneration. With this vision, we have established the Laboratory of Neuropathology of Interorganellar Contact Sites.

X: @floresromeroh