bims-mitran 2026-04-26 papers

Issue of 2026–04–26
two papers selected by
Andreas Kohler, Umeå University

bioRxiv. 2026 Apr 11. pii: 2026.04.09.717523. [Epub ahead of print]

Structural Basis of Mitochondrial Transcription Regulation via Interactions of PolRMT and TFAM with Upstream Promoter DNA.

Rory E Shakey, Caitlin Schroeder, Xiangyu Deng, Jamie Smith, Alfredo J Hernandez, Yang Gao.

Mitochondrial DNA (mtDNA) transcription is essential for cellular energy production and is carried out by a streamlined transcription system in which transcription factor A (TFAM), transcription factor B2 (TFB2M), and the mitochondrial RNA polymerase (PolRMT) assemble at defined promoters to initiate transcription. Previous structural studies elucidated the core initiation mechanism but relied on truncated promoter templates that excluded upstream regulatory DNA interactions. Here, we present two conformations of mitochondrial transcription initiation complexes assembled on the heavy-strand promoter (HSP): a TFAM-bound complex with extended upstream DNA and a TFAM-free complex containing short linear DNA. The TFAM-bound structure reveals a transcription-stimulatory interface between PolRMT and the upstream promoter region (UPR) enabled by TFAM-induced promoter bending. Consistent with this structural observation, UPR truncation reduces transcription from all mtDNA promoters, an effect abolished by mutation of the PolRMT interface. In contrast, the TFAM-free structure reveals a transcription-inhibitory interaction of linear upstream DNA with the PolRMT tether helix, which would sterically clash with TFAM binding. Deletion of the tether helix increases off-target transcription, supporting an autoinhibitory role that enhances promoter specificity. Together, these findings reveal how TFAM-shaped promoter architecture and PolRMT regulatory elements coordinate mitochondrial transcription initiation and regulation.

DOI: https://doi.org/10.64898/2026.04.09.717523

Nat Commun. 2026 Apr 21.

Mitochondrial respirasome-like supercomplexes support metabolic flexibility in yeast.

Mazzen H Eldeeb, Zoe Cosner, Andreas Carlström, Jeffri-Noelle Mays, Gabriella F Rodriguez, Jens Berndtsson, Martin Ott, Flavia Fontanesi.

The mitochondrial respiratory chain (MRC) complexes, crucial for aerobic energy transduction in eukaryotes, form conserved higher-order structures called supercomplexes (SCs). The elucidation of SC physiological relevance is critical for our understanding of mitochondrial function and bioenergetics but has been hindered by the limited availability of experimental models isolating SC formation as the sole variable. In baker's yeast, SCs comprise III2IV1 and III2IV2 configurations, which enhance respiratory rates by facilitating cytochrome c diffusion along the SC surface. However, the roles of distinct SC conformations and MRC plasticity remain unclear. To address these questions, we engineered a yeast strain expressing a covalently-linked III2IV2 SC, structurally like the wild-type. Expression of this tethered SC supports robust respiratory activity but selectively impacts cytosolic NADH-driven respiration, due to distinct interactions with the NADH dehydrogenase Nde1. We propose that in yeast mitochondria, substrate-specific respirasome-like SCs contribute to the optimization of electron fluxes and support metabolic flexibility.

DOI: https://doi.org/10.1038/s41467-026-72228-8