Peer-reviewed publications

Busch JD*, Schöndorf T, Milenkovic D, Li X, Wibom R, Silva-Rodrigues JF, Filograna R, Koolmeister C, Larsson NG, Rubalcava-Gracia D* ✉️. 

The mitochondrial protein TMEM177 fine-tunes mammalian cytochrome c oxidase assembly. doi: 10.1016/j.mito.2025.102099 

Mitochondrion

2025

This study shows that TMEM177 is a mitochondrial protein that fine-tunes complex IV assembly by stabilizing the chaperone COX20 in vivo. Its loss in mice minimally impacts overall OXPHOS function.

Gerlach J*, Pireddu P*, Zhang X, Wetzel S, Mennuni M, Milenkovic D, Nolte H, da Silva Rodrigues F, Branzell N, Kaya I, Garcia Villegas R, Rubalcava-Gracia D, Alsina D, Feederle R, Andrén PE, Langer T, Svenningsson P, Filograna R ✉️. 

The CHCHD2-CHCHD10 protein complex is modulated by mitochondrial dysfunction and alters lipid homeostasis in the mouse brain. doi: 10.1038/s41419-025-08030-z. 

Cell Death & Disease 

2025

In this work, D. Rubalcava-Gracia collaborated with the Filograna Group to investigate the CHCHD2-CHCHD10 complex, revealing its essential role in maintaining motor function and lipid homeostasis in the mouse brain and showing its modulation by mitochondrial dysfunction.

Rubalcava-Gracia D ✉️ , Bubb K, Levander F, Burr S, August AV, Chinnery PF, Koolmeister C, Larsson NG ✉️ .

LRPPRC and SLIRP synergize to maintain sufficient and orderly mammalian mitochondrial translation. doi: 10.1093/nar/gkae662.

Nucleic Acids Research  

2024

In this study, we created mouse lines to study the interaction between the proteins LRPPRC and SLIRP. This work confirmed that these proteins are interdependent for stability and that their complex is crucial for maintaining Complex I levels and regulating tissue-specific mitochondrial translation. I also found that mutations in the LRPPRC-SLIRP interaction site disrupt the translation of Atp8/Atp6 mRNA, highlighting this region's role in gene expression.

Jiang S*, Yuan T*, Rosenberger FA, Mourier A, Dragano NRV, Kremer LS, Rubalcava-Gracia D, Hansen FM, Borg M, Mennuni M, Filograna R, Alsina D, Misic J, Koolmeister C, Papadea P, de Angelis MH, Ren L, Andersson O, Unger A, Bergbrede T, Di Lucrezia R, Wibom R, Zierath JR, Krook A, Giavalisco P, Mann M, Larsson NG ✉️. 

Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity. doi: 10.1038/s42255-024-01038-3

Nature Metabolism

2024

This paper reveals that blocking mitochondrial DNA transcription surprisingly reverses diet-induced fatty liver disease and obesity. The research suggests that disrupting this process in mice leads to a metabolic reprogramming, ultimately improving their overall health.

Pham TCP, Raun SH, Havula E, Henriquez-Olguín C, Rubalcava-Gracia D, Frank E, Fritzen AM, Jannig PR, Andersen NR, Kruse R, Sadek Ali M, Irazoki A, Halling JF, Ringholm S, Needham EJ, Hansen S, Lemminger AK, Schjerling P, Houborg Petersen M, Eisemann de Almeida M, Elbenhardt Jensen T, Kiens B, Hostrup M, Larsen S, Ørtenblad N, Højlund K, Kjær M, Ruas JL, Trifunovic A, Pind Wojtaszewski JF, Nielsen J, Qvortrup K, Pilegaard H, Richter EA, Sylow L ✉️. 

The mitochondrial mRNA stabilizing protein, SLIRP, regulates skeletal muscle mitochondrial structure and respiration by exercise-recoverable mechanisms. doi: 10.1038/s41467-024-54183-4.

Nature Communications 

2024

In this work, D. Rubalcava collaborated with Lykke Sylow's research group at Copenhagen University to explore the role of exercise in alleviating mitochondrial dysfunction in skeletal muscle.

Rubalcava-Gracia D*, García-Villegas R*, Larsson NG ✉️.

No role for nuclear transcription regulators in mammalian mitochondria? doi: 10.1016/j.molcel.2022.09.010.

Molecular Cell

2023

This review challenges the idea that nuclear transcription regulators directly control gene expression within mammalian mitochondria. The main challenge is distinguishing between direct regulation and indirect regulation. The paper provides a critical discussion and experimental guidelines for future research to assess the roles of these factors.

Kremer LS*, Bozhilova LV*, Rubalcava-Gracia D, Filograna R, Upadhyay M, Koolmeister C, Chinnery PF ✉️, Larsson NG ✉️.

A role for BCL2L13 and autophagy in germline purifying selection of mtDNA. doi: 10.1371/journal.pgen.1010573

PLoS Genetics

2023

This paper describes how the BCL2L13 protein and autophagy contribute to purifying selection, the process by which harmful mitochondrial DNA (mtDNA) mutations are eliminated across generations. 

Nieto-Panqueva F, Rubalcava-Gracia D, Hamel PP, González-Halphen D ✉️. 

The constraints of allotopic expression. doi: 10.1016/j.mito.2023.09.004

Mitochondrion

2023 

This paper discusses the constraints of allotopic expression, a technique used to express mitochondrial proteins from the nuclear genome. It explores the challenges and limitations associated with this process, which is crucial for studying mitochondrial function and developing therapies for mitochondrial diseases.

Rubalcava-Gracia D, García-Rincón J, Pérez-Montfort R, Hamel PP, González-Halphen D ✉️. 

Key within-membrane residues and precursor dosage impact the allotopic expression of yeast subunit II of cytochrome c oxidase. doi: 10.1091/mbc.E18-12-0788

Molecular Biology of the Cell

2019 

Here we investigated the successful allotopic expression of subunit II of cytochrome c oxidase in yeast. It identifies that specific amino acid residues and the concentration of the protein's precursor are crucial factors for its proper function and integration when expressed from the nucleus.

Rubalcava-Gracia D, Vázquez-Acevedo M, Funes S, Pérez-Martínez X, González-Halphen D ✉️.

Mitochondrial versus nuclear gene expression and membrane protein assembly: the case of subunit 2 of yeast cytochrome c oxidase. doi: 10.1091/mbc.E17-09-0560

Molecular Biology of the Cell 

2018

This paper examines the allotopic expression of subunit II of cytochrome c oxidase (Cox2) in yeast, a protein normally encoded by mitochondrial DNA. It reveals that while the nucleus-expressed version of Cox2 with a specific W56R mutation can restore respiratory function, its successful integration and maturation are limited by the protein's biogenesis pathway rather than the mutation itself.

Vázquez-Acevedo M, Rubalcava-Gracia D, González-Halphen D  ✉️.

In vitro import and assembly of the nucleus-encoded mitochondrial subunit III of cytochrome c oxidase (Cox3). doi: 10.1016/j.mito.2014.02.005.

Mitochondrion 

2014

This paper shows the successful in vitro import and assembly of Polytomella's nucleus-encoded subunit III of cytochrome c oxidase (Cox3), a protein normally encoded by mitochondrial DNA. This protein follows an energy-dependent import pathway and is functionally assembled into the cytochrome c oxidase complex.

Science communication publications

González-Halphen D, Vázquez-Acevedo M, Vega-Luna F, Rubalcava-Gracia D. 

Evolución de los genomas mitocondriales: transferencia natural y artificial de genes mitocondriales al núcleo. 

Mensaje Bioquímico XLI: 116-126. 

2017

Rubalcava-Gracia D. 

Poder, salud y misterios resueltos. 

FULCRUM 23: 27-28. 

2015