Biology subjects

Niedzwiecka, K.

Publications and source records attributed to Niedzwiecka, K..

2 recordsLinked to original sources

bioRxiv2022

Small Protein Interactome analysis of ATP synthase identifies the uncharacterized 'subunit' Mco10 - a new modulator of permeability transition pore in S. cerevisiae

In S. cerevisiae, the uncharacterized protein Mco10 (Mitochondrial class one protein of 10 kDa) was previously found to be associated with mitochondrial ATP synthase and referred to as a new subunit l. However, recent cryo-EM structures of S. cerevisiae ATP synthase could not ascertain Mco10 as a structural subunit of the enzyme, either monomers or dimers, making questionable its role as a structural subunit. The N-terminal part of Mco10 is very similar to Atp19 (subunit k) of ATP synthase. The subunit k/Atp19, along with the subunits g/Atp20 and e/Atp21 plays a major role in stabilization of the ATP synthase dimers. In our effort to confidently define the small protein interactome of ATP synthase we similarly found Mco10 associated with ATP synthase of S. cerevisiae. We herein investigated the impact of Mco10 on ATP synthase functioning. Biochemical analysis revealed in spite of similarity in sequence and evolutionary lineage, that Mco10 and Atp19 differ significantly in function. This is the first work to show Mco10 is an auxiliary ATP synthase subunit that only functions in permeability transition.

cell biology↗

bioRxiv2022

Mitochondrial membrane potential acts as a retrograde signal to regulate cell cycle progression

Mitochondria are central to numerous anabolic and catabolic pathways whereby mitochondrial dysfunction has a profound impact on metabolism and can manifest in disease. The consequences of mitochondrial dysfunction can be ameliorated by adaptive responses that rely on mito-cellular crosstalk to communicate mitochondrial distress to the rest of the cell. Such mito-cellular signaling slows cell cycle progression in mitochondrial-DNA deficient ({rho}0) Saccharomyces cerevisiae cells, but the initial trigger and the pathway mediating the response has remained unknown. Here, we show that decreased mitochondrial membrane potential ({Delta}{Psi}m) acts as the initial signal of mitochondrial stress that delays G1-to-S phase transition in both {rho}0 and control cells. Accordingly, experimentally increasing {Delta}{Psi}m was sufficient to restore timely cell cycle progression in {rho}0 cells. Neither the RTG retrograde pathway nor central DNA damage checkpoint kinases were involved in mediating this form of mito-cellular communication. The identification of {Delta}{Psi}m as a novel regulator of cell cycle progression may have implications for disease states involving mitochondrial dysfunction.

cell biology↗