Dissecting the regulation of plant mitochondrial metabolism and its impact on cyto-nuclear NAD signaling

• Applicants: Professorin Dr. Iris Finkemeier; Professorin Dr. Veronica Maurino; Professor Dr. Markus Schwarzländer
• Subject Area: Plant Physiology
• Term: since 2016
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 289357231

Mitochondria act as central energy converters in most complex organisms and are deeply embedded into the cellular metabolic network. Mitochondrial metabolism is particularly flexible in plants and can rapidly switch between different programmes to integrate changing environmental conditions. In the previous phase of this project, we investigated physiological dynamics and regulatory mechanisms that operate to re-orchestrate mitochondrial metabolism during dark-light transitions. We identified mitochondrial malate metabolism as a hotspot of flexible ‘remote’ control of cyto-nuclear NAD status. This has consequences not only for subcellular metabolism, but also for cell signalling. In the second phase of this collaborative project we will address the hypothesis that cyto-nuclear NAD status links mitochondrial metabolic flexibility to reprogramming of nuclear gene expression. Bringing together unique expertise from three laboratories we will address the questions of (1) how mitochondrial metabolism modulates cyto-nuclear NAD status, and (2) what impact mitochondria-derived NAD dynamics have on nuclear gene expression. We will modulate mitochondrial malate dehydrogenase (mMDH) and NAD malic enzyme (NAD-ME) capacities by reverse genetics in Arabidopsis to re-route subcellular metabolism. To understand the physiological mechanisms behind mitochondria-controlled modulation of cyto-nuclear NAD status, we will explore the regulation of mMDH and NAD-ME by post-translational modifications and interactors. The impact of the re-routed metabolic flux on cyto-nuclear NAD status will be assessed using in vivo and dynamically fluorescent protein biosensing during dark-light cycles and elicitor exposure, for which we have recently found profound impact on NAD status. Monitoring both, NADH/NAD+ and NAD+ concentration will define NAD in vivo signatures at high precision and inform transcriptomic investigation of NAD signalling, with a focus on the nuclear NAD-dependent deacetylase sirtuin 1 as a potential epigenetic integrator of NAD dynamics. As a result, we will unravel the interface between the flexibility of plant mitochondrial metabolism and signalling programs to choreograph acclimation.

• DFG Programme: Research Grants