DurreShahwar (Durre) Muhammad

Cellular and peroxisomal quality control systems

PhD: North Carolina State University, Raleigh, NC

Postdoctoral Training: Rice University, Houston, TX

Peroxisomes are fascinating metabolic organelles and house numerous reactions required for life in plants and animals. The metabolism and resulting byproducts that occur in peroxisomes are ripe for exploration. A hallmark metabolic reaction in peroxisomes is fatty acid β-oxidation. In mammals, very-long-chain fatty acid β-oxidation occurs in peroxisomes before shorter fatty acids are β-oxidized in mitochondria. In contrast, in plants, all fatty acid β-oxidation occurs in peroxisomes. In non-plant eukaryotes, peroxisomal metabolism also includes plasmalogen synthesis, sterol and bile acid synthesis, and penicillin biosynthesis. Plant peroxisomes also sequester the glyoxylate cycle, which allows pre-photosynthetic seedlings to catabolize stored lipids to synthesize carbohydrates and biosynthesis of phytohormones, including auxin, jasmonic acid, and salicylic acid, which regulate plant growth and development and responses to environmental cues. These same peroxisomal reactions rely on metabolite exchange with other subcellular compartments and generate reactive oxygen species (ROS), including hydrogen peroxide and superoxide radicals, and reactive nitrogen species (RNS), such as nitric oxide.

To maintain intralumenal proteostasis and protect against cellular damage, peroxisomes also contain antioxidant systems that decompose ROS and RNS. When these antioxidant systems are inadequate, protein damage ensues, requiring additional quality control mechanisms. For example, obsolete and damaged peroxisomes are degraded via pexophagy, a specialized form of autophagy.

Despite the importance of peroxisomes and their vital interactions with other essential organelles, knowledge of the mechanisms involved in peroxisome quality control, peroxisome turnover, and the cellular signaling that arises when peroxisomes are dysfunctional is minimal. The Muhammad lab seeks to understand how peroxisomes maintain proteostasis and, by extension, whole-cell homeostasis in a high oxidative stress environment.

Research:

(1) In the Arabidopsis lon protease 2 (lon2) mutant, even functional peroxisomes are targeted for autophagic destruction. The lon2 mutant thus provides a unique platform to identify components regulating pexophagy and cellular signaling responses to heightened or prevented pexophagy. We aim to evaluate the role of LON2 in peroxisome and whole-cell homeostasis.

(2) Arabidopsis has several predicted and confirmed peroxisomal proteases and chaperones that are understudied. One example of both activities is the LON protein, which are ATP-dependent chaperones and proteases that recognize, refold, and/or degrade substrates in bacteria, yeast, mammals, and plants. LON2 contains a peroxisomal-targeting signal. Many eukaryotes, including plants and mammals, contain peroxisomal LON isoforms. Here in the Muhammad lab, we are working to determine the mechanisms governing the fine balance of protein repair and degradation in peroxisomes.

(3) Peroxisomes extensively collaborate with other organelles, and we observed organellar proteome shifts when peroxisomes are dysfunctional and overly degraded. We are assessing the effects on other subcellular compartments stemming from peroxisome dysfunction.

(4) Salt and cadmium (Cd) stress promotes peroxisome proliferation, but neither increases stress tolerance or peroxisome function. We recently found this to be the case for iron (Fe) stress as well. Fe is a micronutrient required for plant growth and development and is bound to functional peroxidases and catalase that localize to peroxisomes. Additionally, iron uptake and utilization must be tightly regulated to maintain homeostasis and prevent iron deficiency or toxicity. We are utilizing Fe stress to elucidate the intricacies of peroxisome dynamics in abiotic stress response.

Our research uses a combination of genetic, molecular, cellular, biochemical, and systems approaches/techniques. We welcome inquiries from prospective undergraduate and graduate students, postdocs, and technicians.

(*equal contributions)

Schmittling S*., Muhammad D*., Haque S., Long T.A., Williams C. (2023) Cellular Clarity: A logistic regression approach to identify root epidermal regulators of iron deficiency response. BMC Genomics. 24: 620.

Muhammad D*., Alameldin H.F*., Oh S., Montgomery B.L., Warpeha K.M. (2023) Arogenate Dehydratases: Unique roles in light-directed development during the seed-to-seedling transition in Arabidopsis thaliana. Frontiers in Plant Science. 14: 1220732. 

Muhammad D*., Smith K.A*., Bartel B. (2022) Plant Peroxisome Proteostasis—Establishing, Renovating, and Dismantling the Peroxisomal Proteome. Essays in Biochemistry. 66: 229–242. 

Muhammad D., Clark N.M., Haque S., Williams C.M., Sozzani R., Long T.A. (2022) POPEYE intercellular localization mediates cell-specific iron deficiency responses. Plant Physiology. 190: 2017-2032. 

Koryachko, A., Matthiadis A., Haque, S., Muhammad D., Ducoste J., Tuck J., Long T.A., Williams C. (2019) Dynamic modeling of iron deficiency response in A. thaliana roots. in silico Plants. 1: diz005

Muhammad D*., Schmittling S*., Williams C., Long T.A. (2016) More than Meets the Eye: Emergent Properties of Transcription Factors Networks in Arabidopsis. BBA Gene Regulatory Mechanisms. 1860: 64-74.

Para A., Muhammad D., Orozco-Nunnelly D., Memishi R., Alvarez S., Naldrett M., Warpeha K. (2016) The dehydratase ADT3 affects ROS homeostasis and cotyledon development. Plant Physiology. 172: 1045-1060.

Koryachko, A., Matthiadis A., Muhammad D., Foret J., Brady S.M., Ducoste J., Tuck J., Long T.A., Williams C. (2015) Clustering and Differential Alignment Algorithm: Identification of early stage regulators in the Arabidopsis thaliana iron deficiency response. PLOS One. 10: e0136591.  

Orozco-Nunnelly D.A., Muhammad, D., Liakaite, V., Green, S., Warpeha K.M. (2014) Pirin1 Is a Non-Circadian Regulated Transcript and Protein, but Highly Responsive to Light/Dark Periods in the Seed-to-Seedling Transition in Arabidopsis thaliana. Plant Molecular Biology Reporter. 33: 1336-1348.

Sullivan, J., Muhammad, D., Warpeha, K.M. (2014) Phenylalanine is required to promote specific developmental responses and prevent cellular damage in response to UV-B in soybean (Glycine max) during the seed-to-seedling transition. PLOS One. 9: e112301.

Orozco-Nunnelly D.A., Muhammad, D., Mezzich R., Lee, B.S., Jayathilaka L., Kaufman L.S., Green, S., Warpeha K.M. (2014) Pirin1 (PRN1) is a multifunctional protein that regulates quercetin, and impacts light and UV responses in the seed-to-seedling transition of Arabidopsis thaliana. PLOS One. 9: e93371.