Biogenesis and quality control of mitochondria

PD Dr. Dejana Mokranjac

Enlarge

+49 89 2180 74220

mokranjac@bio.lmu.de

B02.038

LSM - Graduate School Life Science Munich

Research

Enlarge

We are fascinated by mitochondria and, in particular, how they are made and maintained. Mitochondria contain their own genome and a complete apparatus for its expression, however, this genome encodes only for a handful of mitochondrial proteins. The vast majority of over 1000 different mitochondrial proteins are encoded in the nucleus, synthesized on cytosolic ribosomes as precursor proteins with specific targeting signals and subsequently imported into the organelle. About 60% of mitochondrial proteins are synthesized with N-terminal, positively charged extensions called presequences and are translocated into mitochondria with the help of the TOM and TIM23 complexes in the outer and inner membrane, respectively, along the so-called presequence pathway. This pathway is not only essential for biogenesis of mitochondria but is also used by the cells as a sensitive readout for the functionality of their mitochondria. The majority of our research is centred around the following questions:

1. How do the TOM and TIM23 complexes cooperate during translocation of proteins?

2. How does the TIM23 complex manage to translocate some proteins across and insert the others into the inner membrane?

3. How does the TIM23 complex convert the energy of ATP hydrolysis into unidirectional transport of proteins into mitochondria?

4. How do cells use the presequence pathway to sense the functionality of their mitochondria?

Sometimes our experiments lead us to unexpected areas we never planned to go to but we remain curious and open to explore novel directions. That´s how we recently revealed a novel pathway for introduction of disulfide bonds into inner membrane proteins and started to look into assembly pathways of some of the complexes in the mitochondrial inner membrane. And that is the real beauty of basic science - one never knows where the next experiment will take you!

Methods and approaches

Enlarge

We combine biochemistry with cell biology and yeast genetics and frequently dwell into structural biology and biophysics to reveal molecular mechanisms of biogenesis and quality control of mitochondria and how they are integrated into the physiology of the cell.

Key publications

Bertram N, Izawa T, Thoma F, Schwenkert S, Duvezin-Caubet S, Park SH, Wagener N, Devin A, Osman C, Neupert W, Mokranjac D. (2025) Delayed protein translocation protects mitochondria against toxic CAT-tailed proteins. Mol. Cell 85: 4082–4092. doi: 10.1016/j.molcel.2025.09.030.

Badrie S, Hell K, Mokranjac D. (2025) Dbi1 is an oxidoreductase and an assembly chaperone for mitochondrial inner membrane proteins. EMBO Rep. 26(4):911-928. doi: 10.1038/s44319-024-00349-6.

Genge MG, Roy Chowdhury S, Dohnálek V, Yunoki K, Hirashima T, Endo T, Doležal P, Mokranjac D. (2023) Two domains of Tim50 coordinate translocation of proteins across the two mitochondrial membranes. Life Sci. Alliance 6(12):e202302122. doi: 10.26508/lsa.202302122.

Mapa K, Sikor M, Kudryavtsev V, Waegemann K, Kalinin S, Seidel CAM, Neupert W, Lamb D, Mokranjac D. (2010) The conformational dynamics of the mitochondrial Hsp70 chaperone. Mol. Cell 38: 89-100. doi: 10.1016/j.molcel.2010.03.010.

Popov-Čeleketić D, Mapa K, Neupert W, Mokranjac D. (2008) Active remodeling of the TIM23 complex during translocation of preprotein into mitochondria. EMBO J. 27(10): 1469-1480. doi: 10.1038/emboj.2008.79.

The complete list of our publications can be found at https://pubmed.ncbi.nlm.nih.gov/?term=mokranjac+d&sort=date&size=100

Alumni