Depletion of respiratory chain complexes modulates cristae architecture via MIC10 in human cells

Yarova, Kateryna

dc.contributor.advisor	Jakobs, Stefan Prof. Dr.
dc.contributor.author	Yarova, Kateryna
dc.date.accessioned	2024-10-18T14:11:14Z
dc.date.issued	2024-10-18
dc.identifier.uri	http://resolver.sub.uni-goettingen.de/purl?ediss-11858/15562
dc.identifier.uri	http://dx.doi.org/10.53846/goediss-10809
dc.format.extent	125	de
dc.language.iso	eng	de
dc.subject.ddc	570	de
dc.title	Depletion of respiratory chain complexes modulates cristae architecture via MIC10 in human cells	de
dc.type	doctoralThesis	de
dc.contributor.referee	Jakobs, Stefan Prof. Dr.
dc.date.examination	2024-10-02	de
dc.description.abstracteng	The complex structure of the inner mitochondrial membrane plays a key role in mitochondrial function. The inner mitochondrial membrane is divided into the inner boundary membrane and the cristae membrane, which is characterized by pleomorphic invaginations. The cristae membranes are the main site of oxidative phosphorylation (OXPHOS) as they harbor the complexes involved in cellular respiration, including complexes I-IV of the mitochondrial respiratory chain and ATP synthase. Although the function of F1F0-ATP synthase in stabilizing the cristae rims has been well studied, it remains to be elucidated how the respiratory chain complexes, whose absence often disrupts cristae morphology and leads to severe metabolic diseases, can influence the lamellar morphology of the cristae. To elucidate the potential influence of respiratory chain complexes on the inner mitochondrial membrane, I investigated the recently identified mitochondrial translation factor FAM210A, which has been implicated in mitochondrial inner membrane remodeling. Using CRISPR-Cas9 gene editing, I was able to show that the absence of the FAM210A protein leads to a reduction in the abundance of respiratory chain complexes (RCC). This reduction in RCC leads to the down-regulation of MIC10 from MICOS, affecting the morphology of the inner mitochondrial membrane. Reintroduction of MIC10 into the respiratory chain complex-depleted system restores the wild-type lamellar cristae membrane phenotype, but not mitochondrial respiratory function. In summary, I have elucidated the role of the protein FAM210A as a translational factor in HeLa cells and investigated various functional aspects. I have discovered a previously unknown interdependency between RCC and mitochondrial inner membrane structure mediated by MIC10 human cells. I propose a new regulatory axis in which respiratory chain complexes regulate the abundance of MIC10 and thereby adapt the architecture of the cristae.	de
dc.contributor.coReferee	Thumm, Michael Prof. Dr.
dc.subject.eng	inner mitochondrial membrane	de
dc.subject.eng	respiratory chain complexes	de
dc.subject.eng	MICOS complex	de
dc.subject.eng	cristae membrane	de
dc.subject.eng	mitochondrial morphology	de
dc.subject.eng	oxidative phosphorylation	de
dc.identifier.urn	urn:nbn:de:gbv:7-ediss-15562-3
dc.date.embargoed	2025-10-01
dc.affiliation.institute	Biologische Fakultät für Biologie und Psychologie	de
dc.subject.gokfull	Biologie (PPN619462639)	de
dc.description.embargoed	2025-10-01	de
dc.identifier.ppn	1906290040
dc.notes.confirmationsent	Confirmation sent 2024-10-18T14:15:01	de

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GGNB - Göttinger Graduiertenzentrum für Neurowissenschaften, Biophysik und molekulare Biowissenschaften [1218]
GGNB - Göttingen Graduate Center for Neurosciences, Biophysics and Molecular Biosciences

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